MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Current Protein and Peptide Science' source. Sun, 21 Mar 2010 16:57:52 +0100 http://www.medworm.com/index.php?rid=3361080&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20222865%26dopt%3DAbstract Authors: Varca GH, Andréo-Filho N, Lopes PS, Ferraz HG Cyclodextrins are oligosaccharides, specifically cyclic alpha-1,4-D-glucose oligomers, that possess a cone-like shape resulting in a hydrophobic inner cavity capable of forming complexes with several guest molecules in a hydrophilic matrix. This capability has led to an extensive investigation into cyclodextrin applications in several different substrates with the purpose of overcoming limitations, such as solubility issues, physical degradation and sensitivity to solvents, in guest substances. Researchers have recently described successful interactions between cyclodextrins and proteins, such as enzymes, peptides and amino acids. These complex biomolecules consist of potent active ingredients and are employed in several indus... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=3361080 Fri, 12 Mar 2010 00:00:00 +0100 3361080 http://www.medworm.com/index.php?rid=3339921&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20201794%26dopt%3DAbstract Authors: Baccari MC Orexin A (OXA) and orexin B (OXB) are recently discovered neuropeptides that appear to play a role in various distinct functions such as arousal and the sleep-wake cycle as well as on appetite and regulation of feeding and energy homeostasis. Orexins were first described as neuropeptides expressed by a specific population of neurons in the lateral hypothalamic area, a region classically implicated in feeding behaviour. Orexin neurons project to numerous brain regions, where orexin receptors have been shown to be widely distributed: both OXA and OXB act through two subtypes of receptors (OX1R and OX2R) that belong to the G protein-coupled superfamily of receptors. Growing evidence indicates that orexins act in the central nervous system also to regulate gastrointesti... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=3339921 Thu, 04 Mar 2010 00:00:00 +0100 3339921 http://www.medworm.com/index.php?rid=3284533&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20158453%26dopt%3DAbstract Authors: Sakudo A, Xue G, Kawashita N, Ano Y, Takagi T, Shintani H, Tanaka Y, Onodera T, Ikuta K Prion protein (PrP) gene encodes cellular PrP (PrPC), a glycosylphosphatidylinositol (GPI)-anchored cell membrane protein indispensable for infections of prion, which causes Creutzfeldt-Jakob disease (CJD) in humans, bovine spongiform encephalopathy (BSE) in cattle, and scrapie in sheep. Although PrPC is known to be converted into an abnormal isoform (PrPSc) upon prion infection and play an important role in prion diseases, the mechanisms involved remain unclear, partly due to the insolubility of PrPSc, which prevents experimental biochemical and biophysical analyses. Recently, with improvements in computer power and methods, computer analyses have been contributing more to prion studies. A... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=3284533 Tue, 16 Feb 2010 00:00:00 +0100 3284533 http://www.medworm.com/index.php?rid=3200933&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20088767%26dopt%3DAbstract Authors: Pestana-Calsa MC, Ribeiro IL, Calsa T As eukaryotes, plants include in innate defense antimicrobial peptides (AMP), usually small cysteine or glycine-rich peptides effective against a wide range of pathogens. The main classes of AMPs are represented by alpha/beta-defensins, lipid-transfer proteins, thionins, cyclotides, snakins and hevein-like, according to amino acid sequence homology. In spite of increasing number of described AMPs from plants, last decade advances in methodologies for gene expression and the huge amounts of genomic, proteomic and other "-omics" data lead to new prospection strategies of novel potential candidates. Organised user-friendly databases are available to be searched and enlarged with newly discovered plant-derived AMPs. Bioinformatics has allowed ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=3200933 Thu, 21 Jan 2010 00:00:00 +0100 3200933 http://www.medworm.com/index.php?rid=3200932&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20088768%26dopt%3DAbstract Authors: da Rocha Pitta MG, da Rocha Pitta MG, Galdino SL All living organisms, ranging from microorganisms to plants and mammals, have evolved mechanisms to actively defend themselves against pathogen attack. A wide range of biological activities have been attributed to plant antimicrobial peptides (AMPs) including growth inhibitory effects on a broad range of fungi, Gram-positive and Gram-negative bacteria, viruses, neoplasic cells and parasitic protozoa. Classes of AMPs, their mechanisms of action, biological activity, and cytotoxicity towards host cells are discussed. A particular focus regards AMP candidates with potential for use in defense against biological warfare agents. This field is young, but provides additional stimulus to consideration of these molecules as a new class o... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=3200932 Thu, 21 Jan 2010 00:00:00 +0100 3200932 http://www.medworm.com/index.php?rid=3200931&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20088769%26dopt%3DAbstract Authors: Padovan L, Scocchi M, Tossi A EST (Expressed Sequence Tags) databases are increasing in number and size, especially regarding cultivated plants. Sugarcane is one of the most important tropical and subtropical crops, presenting a complex polyploid genome of hybrid origin, bearing a challenge for the understanding of genetic processes in higher plants. In the present work a general search was carried out on the largest Sugarcane EST Database (SUCEST) that includes 237,954 ESTs aiming to identify defensin antimicrobial peptides - a class of small, basic, cysteine-rich peptides distributed throughout the kingdoms. Using a computational approach 17 new defensin isoforms could be identified. Main steps for the search, characterization and evaluation of the defensin expression profil... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=3200931 Thu, 21 Jan 2010 00:00:00 +0100 3200931 http://www.medworm.com/index.php?rid=3200930&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20088770%26dopt%3DAbstract Authors: Padovan L, Crovella S, Tossi A, Segat L To defend themselves from attack by pathogens, plants can rely only on their innate defense systems. Defensins are antimicrobial peptides that contribute to plant immunity by displaying a direct cidal activity against various pathogens, some of which are responsible for plant diseases. These determine a significant decrease in the quality and safety of agricultural products, especially among food crops, and cause significant economic losses. There is consequently an increasing interest for antimicrobial compounds such as the defensins, which might be applied in different ways to protect important food or bio-fuel crops. In this review we analyse the techniques that have been reported in the literature for the production of isolated plant... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=3200930 Thu, 21 Jan 2010 00:00:00 +0100 3200930 http://www.medworm.com/index.php?rid=3200929&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20088771%26dopt%3DAbstract Authors: Kido EA, Pandolfi V, Houllou-Kido LM, Andrade PP, Marcelino FC, Nepomuceno AL, Abdelnoor RV, Burnquist WL, Benko-Iseppon AM Defensin, thionin and lipid transfer protein (LTP) gene families, which antimicrobial activity has an attractive use in protein engineering and transgenic production of agronomical important plants, have been here functionally reviewed. Also, a transcriptional overview of a set of plant SuperSAGE libraries and analysis looking for 26 bp tags possibly annotated for those families is presented. Tags differentially expressed (p = 0.05) or constitutively transcribed were identified from leaves or roots SuperSAGE libraries from important Brazilian plant species [cowpea (Vigna unguiculata (L.) Walp.), soybean (Glycine max (L.) Merr.) and modern sugarcane hybrid... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=3200929 Thu, 21 Jan 2010 00:00:00 +0100 3200929 http://www.medworm.com/index.php?rid=3200928&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20088772%26dopt%3DAbstract Authors: Benko-Iseppon AM, Galdino SL, Calsa T, Kido EA, Tossi A, Belarmino LC, Crovella S Mechanisms related to biotic interactions, such as pathogen attack, herbivory and symbiosis are important challenges to higher plants and have been widely studied especially for breeding purposes. The present review focuses on a special category of defense molecules, the plant antimicrobial peptides, providing an overview of their main molecular features and structures. PMID: 20088772 [PubMed - as supplied by publisher] (Source: Current Protein and Peptide Science) Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=3200928 Thu, 21 Jan 2010 00:00:00 +0100 3200928 http://www.medworm.com/index.php?rid=3200927&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20088773%26dopt%3DAbstract Authors: Belarmino C, Capriles PV, Crovella S, Dardene LE, Benko-Iseppon AM EST (Expressed Sequence Tags) databases are increasing in number and size, especially regarding cultivated plants. Sugarcane is one of the most important tropical and subtropical crops, presenting a complex polyploid genome of hybrid origin, bearing a challenge for the understanding of genetic processes in higher plants. In the present work a general search was carried out on the largest Sugarcane EST Database (SUCEST) that includes 237,954 ESTs aiming to identify defensin antimicrobial peptides - a class of small, basic, cysteine-rich peptides distributed throughout the kingdoms. Using a computational approach 17 new defensin isoforms could be identified. Main steps for the search, characterization and evaluat... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=3200927 Thu, 21 Jan 2010 00:00:00 +0100 3200927 http://www.medworm.com/index.php?rid=3200926&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20088774%26dopt%3DAbstract Authors: Belarmino LC, Benko-Iseppon AM The expressive amount of nucleotide sequences from diverse plant species in databanks enables the use of computational approaches to discovery still unidentified genes and to infer about their function, structure and role in some biological processes. Of special interest are the antimicrobial peptides (AMP), whose functionalities have a very important role in defense against microbial infection in multicellular eukaryotes, being considered less susceptible to bacterial resistance than traditional antibiotics, with potential to develop a new class of therapeutic agents. Recent computational developments have provided various algorithms and resources to profit from the overwhelming information in data banks for biomining such peptides. This review ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=3200926 Thu, 21 Jan 2010 00:00:00 +0100 3200926 http://www.medworm.com/index.php?rid=3200925&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20088775%26dopt%3DAbstract Authors: Alguel Y, Leung J, Singh S, Rana R, Civiero L, Alves C, Byrne B The last five years have seen a dramatic increase in the number of membrane protein structures. The vast majority of these 191 unique structures are of membrane proteins from prokaryotic sources. Whilst these have provided unprecedented insight into the mechanism of action of these important molecules our understanding of many clinically important eukaryotic membrane proteins remains limited by a lack of high resolution structural data. It is clear that novel approaches are required to facilitate the structural characterization of eukaryotic membrane proteins. Here we review some of the techniques developed recently which are having a major impact on the way in which structural studies of eukaryotic membrane prote... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=3200925 Thu, 21 Jan 2010 00:00:00 +0100 3200925 http://www.medworm.com/index.php?rid=3200924&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20088776%26dopt%3DAbstract Authors: Vas M, Varga A, Graczer E Coupling of structural flexibility and biological function is an essential feature of proteins. The role of relative domain movements in enzyme function has been evidenced in many cases. However, the way of communication between protein domains and its manifestation in their movements as well as in the biological function are rarely delineated. In this review we summarize comprehensive studies with a typical hinge-bending two-domain enzyme, 3-phosphoglycerate kinase. A possible mechanism is proposed by which the two substrates that bind to different domains trigger the operation of the molecular hinges, located in the interdomain region. Various crystal structures of the enzyme have been determined with different relative domain positions, suggesting ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=3200924 Thu, 21 Jan 2010 00:00:00 +0100 3200924 http://www.medworm.com/index.php?rid=2546342&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19538139%26dopt%3DAbstract Authors: Kuznetsov IB Conformational flexibility is an inherent property of the protein structure. Large scale changes in the protein conformation play a key role in a variety of fundamental biological activities and have been implicated in a number of diseases. The time scales of functionally relevant dynamic processes in proteins generally do not allow the researchers to study them by the means of detailed atomic level simulations. Therefore, less computationally demanding methods based on the coarse grained models of protein structure and bioinformatics approaches are particularly important for the flexibility-related studies. This review is focused on two broad categories of protein flexibility - protein disorder and conformational switches. In the case of protein disorder, a flexi... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546342 Sun, 28 Jun 2009 03:42:39 +0100 2546342 http://www.medworm.com/index.php?rid=2546341&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19538140%26dopt%3DAbstract Authors: Trivedi MV, Laurence JS, Siahaan TJ There has been a tremendous increase in the number of approved drugs derived from recombinant proteins; however, their development as potential drugs has been hampered by their instability that causes difficulty to formulate them as therapeutic agents. It has been shown that the reactivity of thiol and disulfide functional groups could catalyze chemical (i.e., oxidation and beta-elimination reactions) and physical (i.e., aggregation and precipitation) degradations of proteins. Because most proteins contain a free Cys residue or/and a disulfide bond, this review is focused on their roles in the physical and chemical stability of proteins. The effect of introducing a disulfide bond to improve physical stability of proteins and the mechanisms o... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546341 Sun, 28 Jun 2009 03:42:37 +0100 2546341 http://www.medworm.com/index.php?rid=2546340&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19538141%26dopt%3DAbstract Authors: Ng TB, Wong JH, Wang H The intent of this article is to review recent literature on ribosome inactivating proteins (RIPs) including isolation and characterization of new RIPs, studies on the crystal structures and mechanisms of actions of RIPs, the use of saporin-based neurotoxins to selectively lesion cholinergic neurons in neuroscience research, and the use of RIP-based conjugates and immunotoxins in anticancer therapy. PMID: 19538141 [PubMed - as supplied by publisher] (Source: Current Protein and Peptide Science) Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546340 Sun, 28 Jun 2009 03:42:35 +0100 2546340 http://www.medworm.com/index.php?rid=2546339&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19538142%26dopt%3DAbstract Authors: Nadimpalli SK, Amancha PK Lysosomal enzymes undergo phosphorylation on their mannose residues in the Golgi apparatus and are recognized by two distinct type I transmembrane glycoproteins designated as the mannose 6-phosphate receptors; MPR300, (Mr 300 kDa) and MPR46, (Mr 46 kDa) that internally transport them to the lysosomes. In humans, absence of this recognition system leads to severe lysosomal storage disease, emphasizing their essential role in the biogenesis of lysosomes. Among the two receptors only MPR46 shows an absolute requirement for divalent metal ions. Only MPR300 is known to be a multifunctional protein that also binds many other ligands such as the human IGF-II, thyroglobulin, retinoic acid, granzyme A and B. In mammals, the extracytoplasmic domain of MPR300 pr... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546339 Sun, 28 Jun 2009 03:42:33 +0100 2546339 http://www.medworm.com/index.php?rid=2546338&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19538143%26dopt%3DAbstract Authors: Groenning M, Frokjaer S, Vestergaard B The therapeutic importance of gaining a thorough knowledge on insulin fibrillation in relation to type I diabetes has lead to six decades of studies focusing on its formation kinetics and structural characteristics. Insulin fibrils feature characteristics common to amyloid fibrils such as an elongated morphology, characteristic cross-beta diffraction pattern, Thioflavin T fluorescence, and Congo Red birefringence. A full understanding of the fibrillation process requires structural elucidation of every species and determination of the kinetics of interconversion between species on the reaction pathway. Therefore, describing the underlying mechanism is complicated and different mechanisms have been proposed. In the recent years increased k... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546338 Sun, 28 Jun 2009 03:42:31 +0100 2546338 http://www.medworm.com/index.php?rid=2546337&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19538144%26dopt%3DAbstract Authors: Walter ED, Stevens DJ, Spevacek AR, Visconte MP, Dei Rossi A, Millhauser GL Current research suggests that the function of the prion protein (PrP) is linked to its ability to bind copper. PrP is implicated in copper regulation, copper buffering and copper-dependent signaling. Moreover, in the development of prion disease, copper may modulate the rate of protein misfolding. PrP possesses a number of copper sites, each with distinct chemical characteristics. Most studies thus far have concentrated on elucidating chemical features of the octarepeat region (residues 60-91, hamster sequence), which can take up to four equivalents of copper, depending on the ratio of Cu2+ to protein. However, other sites have been proposed, including those at histidines 96 and 111, which are adjacen... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546337 Sun, 28 Jun 2009 03:42:29 +0100 2546337 http://www.medworm.com/index.php?rid=2546336&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19538145%26dopt%3DAbstract Authors: Baden EM, Sikkink LA, Ramirez-Alvarado M Systemic light chain amyloidosis (AL) is one of several protein misfolding diseases and is characterized by extracellular deposition of immunoglobulin light chains in the form of amyloid fibrils [1]. Immunoglobulin (Ig) proteins consist of two light chains (LCs) and two heavy chains (HCs) that ordinarily form a heterotetramer which is secreted by a plasma cell. In AL, however, a monoclonal plasma cell population produces an abundance of a pathogenic LC protein. In this case, not all of the LCs pair with the HCs, and free LCs are secreted into circulation. The LC-HC dimer is very stable, and losing this interaction may result in an unstable LC protein [2]. Additionally, somatic mutations are thought to cause amyloidogenic proteins to be ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546336 Sun, 28 Jun 2009 03:42:27 +0100 2546336 http://www.medworm.com/index.php?rid=2546335&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19538146%26dopt%3DAbstract Authors: Uversky VN, Eliezer D Parkinson's disease (PD) is a slowly progressive movement disorder that results from the loss of dopaminergic neurons in the substantia nigra, a small area of cells in the mid-brain. PD is a multifactorial disorder with unknown etiology, in which both genetic and environmental factors play important roles. Substantial evidence links alpha-synuclein, a small highly conserved presynaptic protein with unknown function, to both familial and sporadic PD. Rare familial cases of PD are associated with missense point mutations in alpha-synuclein, or with the hyper-expression of the wild type protein due to its gene duplication/triplication. Furthermore, alpha-synuclein was identified as the major component of amyloid fibrils found in Lewy body and Lewy neurites, ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546335 Sun, 28 Jun 2009 03:42:25 +0100 2546335 http://www.medworm.com/index.php?rid=2546334&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19538147%26dopt%3DAbstract Authors: Chen E, Goldbeck RA, Kliger DS In a 1998 collaboration with Tony Fink, we coupled nanosecond circular dichroism methods (TRCD) with a CO-photolysis system for quickly triggering folding in cytochrome c (cyt c) in order to make the first time-resolved far-UV CD measurement of early secondary structure formation in a protein. The small signal observed in that initial study, approximately 10% of native helicity, became the seed for increasingly robust results from subsequent studies bringing additional natural and magnetic circular polarization dichroism and optical rotatory dispersion detection methods (e.g., TRORD, TRMCD, and TRMORD), coupled to fast photolysis and photoreduction triggers, to the study of early folding events. Nanosecond polarization methods are reviewed here i... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546334 Sun, 28 Jun 2009 03:42:23 +0100 2546334 http://www.medworm.com/index.php?rid=2546333&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19538148%26dopt%3DAbstract Authors: Seshadri S, Oberg KA, Uversky VN Protein aggregation, being one of the hottest topics of modern protein science, is recognized now as a serious biomedical and biotechnological problem. Protein aggregation is considered as a causative factor (or at least an associated symptom) of a wide spectrum of human pathologies. Furthermore, aggregation and precipitation are known to trammel recombinant protein production, as well as to affect the manufacture, storage and delivery of proteinaceous drugs. Therefore, this topic attracts the serious attention of many researchers, a conclusion that follows from the average daily publication of 7-8 scientific papers dedicated to the various aspects of protein aggregation. However, the situation was rather different 15-20 years ago when it was b... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546333 Sun, 28 Jun 2009 03:42:21 +0100 2546333 http://www.medworm.com/index.php?rid=2546332&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19538149%26dopt%3DAbstract Authors: Livermore DM beta-Lactamases are the greatest single source of resistance to beta-lactam antibiotics. For over 60 years, clinicians have seen a pattern whereby useful new beta-lactam analogues are introduced but then select for new beta-lactamases that cause resistance. Thus, penicillin G was undermined by swift accumulation of staphylococcal penicillinase, ampicillin by TEM-1 enzyme and modern oxymino cephalosporins by "extended-spectrum" beta-lactamases. Tony Fink's work contributed greatly to our understanding of the mechanisms and active site function of beta-lactamases and this knowledge now informs the search for new beta-lactams and beta-lactamase inhibitors. PMID: 19538149 [PubMed - as supplied by publisher] (Source: Current Protein and Peptide Science) Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546332 Sun, 28 Jun 2009 03:42:19 +0100 2546332 http://www.medworm.com/index.php?rid=2546331&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19538150%26dopt%3DAbstract Authors: Dunn BM, Uversky VN Knowledge of the existence and structure of intermediates on the reaction pathway is necessary before specific details of the mechanism may be successfully resolved. However, enzymatic catalysis is an extremely fast process. This rapidity of enzyme-catalyzed reactions and the short life times of intermediates represent a major problem in studying the dynamic processes which occur during catalysis, as they prevent the accumulation of intermediates under normal conditions for concentrations and time periods required by most high-resolution structural methods. Therefore, a method that would utilize specific substrates but would permit the detection and characterization of intermediates was highly desired. As one of the approaches to overcome this problem the u... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546331 Sun, 28 Jun 2009 03:42:17 +0100 2546331 http://www.medworm.com/index.php?rid=2546330&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19538151%26dopt%3DAbstract Authors: Uversky VN, Goto Y In a Nature article published in 1993, Anthony L. Fink and colleagues reported how Hsp70 chaperones use ATP binding in the presence of K+, rather than hydrolysis, to accelerate substrate release. As of the summer of 2008, his article had received 297 citations. I discuss here the influence Tony's iconic article has had on the chaperone field. PMID: 19538151 [PubMed - as supplied by publisher] (Source: Current Protein and Peptide Science) Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546330 Sun, 28 Jun 2009 03:42:15 +0100 2546330 http://www.medworm.com/index.php?rid=2546329&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19538152%26dopt%3DAbstract Authors: Witt SN In a Nature article published in 1993, Anthony L. Fink and colleagues reported how Hsp70 chaperones use ATP binding in the presence of K+, rather than hydrolysis, to accelerate substrate release. As of the summer of 2008, his article had received 297 citations. I discuss here the influence Tony's iconic article has had on the chaperone field. PMID: 19538152 [PubMed - as supplied by publisher] (Source: Current Protein and Peptide Science) Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546329 Sun, 28 Jun 2009 03:42:13 +0100 2546329 http://www.medworm.com/index.php?rid=2546328&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19538153%26dopt%3DAbstract Authors: Sharma SK, Christen P, Goloubinoff P Stress, molecular crowding and mutations may jeopardize the native folding of proteins. Misfolded and aggregated proteins not only loose their biological activity, but may also disturb protein homeostasis, damage membranes and induce apoptosis. Here, we review the role of molecular chaperones as a network of cellular defenses against the formation of cytotoxic protein aggregates. Chaperones favour the native folding of proteins either as "holdases", sequestering hydrophobic regions in misfolding polypeptides, and/or as "unfoldases", forcibly unfolding and disentangling misfolded polypeptides from aggregates. Whereas in bacteria, plants and fungi Hsp70/40 acts in concert with the Hsp100 (ClpB) unfoldase, Hsp70/40 is the only known chaperone ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546328 Sun, 28 Jun 2009 03:42:11 +0100 2546328 http://www.medworm.com/index.php?rid=2546327&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19538154%26dopt%3DAbstract Authors: Fisher JF, Mobashery S The discovery that the mechanism of beta-lactam hydrolysis catalyzed by the class A (active site serine-dependent) beta-lactamases proceeds via an acyl-enzyme intermediate was made thirty years ago. Since this discovery, the active site circumstance that enables acylation of the active site serine and further enables hydrolytic deacylation of the acyl-serine intermediate, have received extraordinary scrutiny. The justification for this scrutiny is the direct relevance of the beta-lactamases to the manifestation of bacterial resistance to the beta-lactam antibiotics, and the subsequent (to the discovery of the beta-lactamase acyl-enzyme) recognition of the direct evolutionary relationship between the serine beta-lactamase acyl-enzyme, and the penicillin b... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546327 Sun, 28 Jun 2009 03:42:09 +0100 2546327 http://www.medworm.com/index.php?rid=2546326&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19538155%26dopt%3DAbstract Authors: Petsko GA During the past thirty years significant contributions to our understanding of the structural origins of the catalytic power of enzymes have come from solution and crystallographic studies of enzyme-substrate and enzyme-intermediate complexes trapped at subzero temperatures, a field that was pioneered in large part by Anthony L. Fink and Pierre Douzou. Here I review, from a personal perspective, the history of crystallographic cryoenzymology, with an emphasis on the contributions of Tony Fink. The story has a moral: if you choose your collaborators based not only on their scientific prowess but also on their human qualities, the resulting friendships will enrich your life. PMID: 19538155 [PubMed - as supplied by publisher] (Source: Current Protein and Peptide Sci... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546326 Sun, 28 Jun 2009 03:42:07 +0100 2546326 http://www.medworm.com/index.php?rid=2546325&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19538156%26dopt%3DAbstract Authors: McCormack AL, Di Monte DA When caused by multiplication mutations of its gene, increased expression of alpha-synuclein is associated with familial parkinsonism. Here we discuss the possibility that other mechanisms of alpha-synuclein elevation contribute to the pathogenesis of idiopathic, sporadic Parkinson's disease and other human synucleinopathies. Environmental (e.g. toxic exposures) and genetic (e.g. gene polymorphisms) risk factors, on the background of normal aging, are likely to enhance vulnerability to neurodegenerative processes. Current evidence suggests that an increased level of neuronal alpha-synuclein may represent a key pathogenetic event common to these risk factors. Higher protein expression could underlie a gain of toxic properties of alpha-synuclein (e.g. e... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546325 Sun, 28 Jun 2009 03:42:05 +0100 2546325 http://www.medworm.com/index.php?rid=2546348&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519451%26dopt%3DAbstract Authors: Harauz G, Libich DS The myelin basic protein (MBP) family comprises a variety of developmentally-regulated members arising from different transcription start sites, differential splicing, and post-translational modifications. The "classic" isoforms of MBP include the 18.5 kDa form, which predominates in adult human myelin and facilitates compaction of the mature myelin sheath in the central nervous system, thereby maintaining its structural integrity. In addition to membrane-association, the 18.5 kDa and all other classic isoforms are able to interact with a multitude of proteins, including Ca(2+)-calmodulin, actin, tubulin, and SH3-domain containing proteins, and thus may be signalling linkers during myelin development and remodelling. All proteins in this family are intrinsi... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546348 Sun, 31 May 2009 23:00:00 +0100 2546348 http://www.medworm.com/index.php?rid=2546347&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519452%26dopt%3DAbstract Authors: Kihara D, Chen H, Yang YD Computational protein tertiary structure prediction has made significant progress over the last decade due to the advancement of techniques and the growth of sequence and structure databases. However, it is still not very easy to predict the accuracy of a given predicted structure. Predicting the accuracy, or quality assessment of a prediction model, is crucial for a practical use of the model such as biochemical experimental design and drug design. Recently several model quality assessment programs (MQAPs) have been proposed for assessing global and local accuracy of predicted structures. We will start with reviewing the current status of protein structure prediction methods with an emphasis on the source of errors. Then existing MQAPs are classified... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546347 Sun, 31 May 2009 23:00:00 +0100 2546347 http://www.medworm.com/index.php?rid=2546346&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519453%26dopt%3DAbstract We describe the difficulties in calculating these quantities and review recent methodological developments. Because protein flexibility is essential for function and ligand binding, we discuss the related problems involved in the definition, simulation, and free energy calculation of microstates (such as the alpha-helical region of a peptide). While the review is broad, a special emphasize is given to methods for calculating the absolute F (S), where our HSMC(D) method is described in some detail. PMID: 19519453 [PubMed - in process] (Source: Current Protein and Peptide Science) Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546346 Sun, 31 May 2009 23:00:00 +0100 2546346 http://www.medworm.com/index.php?rid=2546345&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519454%26dopt%3DAbstract Authors: Miller M Large volumes of protein sequence and structure data acquired by proteomic studies led to the development of computational bioinformatic techniques that made possible the functional annotation and structural characterization of proteins based on their primary structure. It has become evident from genome-wide analyses that many proteins in eukaryotic cells are either completely disordered or contain long unstructured regions that are crucial for their biological functions. The content of disorder increases with evolution indicating a possibly important role of disorder in the regulation of cellular systems. Transcription factors are no exception and several proteins of this class have recently been characterized as premolten/molten globules. Yet, mammalian cells rely o... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546345 Sun, 31 May 2009 23:00:00 +0100 2546345 http://www.medworm.com/index.php?rid=2546344&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519455%26dopt%3DAbstract Authors: Qu X, Swanson R, Day R, Tsai J Template based protein structure prediction (commonly referred to as homology or comparative modeling) uses knowledge of solved structures to model a protein sequence's native or true fold. First, a parent structure is found and then a template structure is built by mapping the target sequence onto the parent structure. This putative structure is refined using a combination of backbone moves, side-chain packing, and loop modeling. Template based protein structure prediction has always held great promise to produce atomically accurate models close to the native conformation based on two major assumptions. First, similar sequences exhibit similar protein folds. Second, soluble proteins populate a discrete fold space with many representatives alread... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546344 Sun, 31 May 2009 23:00:00 +0100 2546344 http://www.medworm.com/index.php?rid=2546343&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519456%26dopt%3DAbstract Authors: Sieker F, May A, Zacharias M Major Histo-Compatibility (MHC) class I molecules are major agents of the mammalian adaptive immune system. Class I molecules bind short antigenic peptides with a length of 8-10 residues in the Endoplasmatic Reticulum (ER) and after transport to the cell surface the peptides are presented to T-lymphocytes. The binding site of class I molecules is formed by a deep cleft between two alpha-helices at top of an extended beta-sheet. Only tightly bound high-affinity peptides have a chance to reach the cell surface and trigger an immune response. It is therefore of great interest to identify possible high-affinity antigenic peptides that could be used as vaccines to help the immune system to detect viral infections or kill malignant cells. A large number ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2546343 Sun, 31 May 2009 23:00:00 +0100 2546343 http://www.medworm.com/index.php?rid=2323909&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355977%26dopt%3DAbstract Authors: De Benedetti PG PMID: 19355977 [PubMed - in process] (Source: Current Protein and Peptide Science) Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2323909 Wed, 01 Apr 2009 04:00:00 +0100 2323909 http://www.medworm.com/index.php?rid=2323907&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355978%26dopt%3DAbstract Authors: Onaran HO, Costa T Proteins in their native folded states can possess multiple energy minima and they can show constant conformational fluctuations at physiological temperatures. In this article, we discuss the quantitative relationship between ligand-induced perturbation of such fluctuations, modeled as probability distributions of conformational substates, and allosteric coupling of ligand binding to different sites, as defined by linkage thermodynamics. We show that allosteric coupling between two binding events on the same protein is an inevitable consequence of ligand-induced perturbations of the probability distribution that represents conformational fluctuations in thermal equilibrium. When high resolution structural data of a protein in empty and ligand-bound forms are... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2323907 Wed, 01 Apr 2009 04:00:00 +0100 2323907 http://www.medworm.com/index.php?rid=2323905&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355979%26dopt%3DAbstract Authors: Whitley MJ, Lee AL The phenomenon of intra-protein communication is fundamental to such processes as allostery and signaling, yet comparatively little is understood about its physical origins despite notable progress in recent years. This review introduces contemporary but distinct frameworks for understanding intra-protein communication by presenting both the ideas behind them and a discussion of their successes and shortcomings. The first framework holds that intra-protein communication is accomplished by the sequential mechanical linkage of residues spanning a gap between distal sites. According to the second framework, proteins are best viewed as ensembles of distinct structural microstates, the dynamical and thermodynamic properties of which contribute to the experimental... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2323905 Wed, 01 Apr 2009 04:00:00 +0100 2323905 http://www.medworm.com/index.php?rid=2323903&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355980%26dopt%3DAbstract Authors: Zheng W, Brooks BR, Thirumalai D Allostery forms the basis of intra-molecular communications in various enzymes, however the underlying conformational changes are largely elusive. Recently, we have proposed to employ an elastic model based normal mode analysis to investigate the allosteric transitions in several molecular nanomachines (including myosin II, DNA polymerase and chaperonin GroEL). After combining with bioinformatics analysis of the evolutionary sequence variations, we have been able to identify the highly conserved and robust modes of collective motions that are capable of transmitting molecular signals over long distances. PMID: 19355980 [PubMed - in process] (Source: Current Protein and Peptide Science) Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2323903 Wed, 01 Apr 2009 04:00:00 +0100 2323903 http://www.medworm.com/index.php?rid=2323901&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355981%26dopt%3DAbstract Authors: Lenaerts T, Schymkowitz J, Rousseau F Transducing environmental signals from the cell surface to the nucleus in order to evoke appropriate gene regulatory response requires an accurate and robust medium to propagate biological information. The structure of proteins and especially the dynamic properties of these structures allows for the uptake and restitution of biological information from and to the environment. To understand the functioning and regulation of signalling pathways we therefore have to understand how protein structures encode biological information. Towards this goal several computational methods have been carried out over the last years. First we will provide an overview of these in silico approaches. Next, using the well known SH2 domain as a case study, we de... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2323901 Wed, 01 Apr 2009 04:00:00 +0100 2323901 http://www.medworm.com/index.php?rid=2323899&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355982%26dopt%3DAbstract Authors: Vishveshwara S, Ghosh A, Hansia P Communication within and across proteins is crucial for the biological functioning of proteins. Experiments such as mutational studies on proteins provide important information on the amino acids, which are crucial for their function. However, the protein structures are complex and it is unlikely that the entire responsibility of the function rests on only a few amino acids. A large fraction of the protein is expected to participate in its function at some level or other. Thus, it is relevant to consider the protein structures as a completely connected network and then deduce the properties, which are related to the global network features. In this direction, our laboratory has been engaged in representing the protein structure as a network of... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2323899 Wed, 01 Apr 2009 04:00:00 +0100 2323899 http://www.medworm.com/index.php?rid=2323896&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355983%26dopt%3DAbstract Authors: Antal MA, Böde C, Csermely P The network paradigm is increasingly used to describe the dynamics of complex systems. Here we review the current results and propose future development areas in the assessment of perturbation waves, i.e. propagating structural changes in amino acid networks building individual protein molecules and in protein-protein interaction networks (interactomes). We assess the possibilities and critically review the initial attempts for the application of game theory to the often rather complicated process, when two protein molecules approach each other, mutually adjust their conformations via multiple communication steps and finally, bind to each other. We also summarize available data on the application of percolation theory for the prediction of ami... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2323896 Wed, 01 Apr 2009 04:00:00 +0100 2323896 http://www.medworm.com/index.php?rid=2323893&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355984%26dopt%3DAbstract Authors: Fanelli F, De Benedetti PG, Raimondi F, Seeber M Intramolecular and intermolecular communication is a privileged issue in G protein-Coupled Receptor (GPCR) function as the prominent role of these receptors is to respond to extracellular signals by catalyzing nucleotide exchange in intracellular G proteins. In the last decade or so we have applied much effort in elaborating computational strategies to infer the mechanisms of intramolecular and intermolecular communication in a number of GPCRs of the rhodopsin family. In this article, we review the most relevant achievements on the matter. In summary, the receptor sites of activating mutations or ligand-binding communicate with a common allosteric site in the cytosolic domains. This was inferred from the observation that local p... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2323893 Wed, 01 Apr 2009 04:00:00 +0100 2323893 http://www.medworm.com/index.php?rid=2323890&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355985%26dopt%3DAbstract Authors: De Benedetti PG, Fanelli F Ligand-protein and protein-protein interactions play a pivotal role in any cellular process and function by means of complex and dynamic mechanisms that involve sophisticated intra- and intermolecular communication pathways. The deeper understanding of the molecular and structural mechanisms of these pathways of chemical information transfer constitutes the foundations of rational druggable target discovery and drug design. In this context the role of both molecular recognition/communication between the interacting partners and their quantitative/dynamic description constitute the crucial point. In this respect, many approaches at different level of complexity have been developed and applied to different druggable target like enzymes, membrane recept... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2323890 Wed, 01 Apr 2009 04:00:00 +0100 2323890 http://www.medworm.com/index.php?rid=2257622&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275666%26dopt%3DAbstract Authors: Leung PS, de Gasparo M PMID: 19275666 [PubMed - in process] (Source: Current Protein and Peptide Science) Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2257622 Sun, 01 Feb 2009 05:00:00 +0100 2257622 http://www.medworm.com/index.php?rid=2257621&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275667%26dopt%3DAbstract Authors: Ukkola O Ghrelin is a gut-brain peptide that has somatotropic, food intake increasing and adipogenic effects. Ghrelin is involved in modulating insulin and glucose metabolism in rodents according to recent studies. In humans acylated ghrelin reduces insulin sensitivity while unacylated ghrelin has opposite effects. In general, ghrelin seems to have diabetogenic effects. Obese, in particular abdominally obese, subjects have low ghrelin levels and decreased total ghrelin levels have been associated with metabolic syndrome and Type 2 diabetes. Most of the human studies in Type 1 diabetes have reported low ghrelin levels probably as a compensatory mechanism against hyperglycaemia. The data on obestatin in the regulation of energy balance is extremely contradictory. Interestingly, ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2257621 Sun, 01 Feb 2009 05:00:00 +0100 2257621 http://www.medworm.com/index.php?rid=2257620&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275668%26dopt%3DAbstract Authors: Anuradha CV Emerging evidence suggests that amino acids may be potentially important in the prevention of diabetes and diabetes-associated complications. The pathways involved in the pathogenesis of diabetic complications include increased polyol pathway flux, increased advanced glycation end products formation, activation of protein kinase C and oxidative and carbonyl stress. This review will discuss the modulatory effects of amino acids on insulin secretion and their action in concert with insulin as signaling molecules. Evidences for the role of some amino acids in controlling glycemia and glucose-triggered pathological pathways are also included. Individual amino acids, especially the ones bestowed with antioxidant property like N-acetyl cysteine and taurine seem to have b... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2257620 Sun, 01 Feb 2009 05:00:00 +0100 2257620 http://www.medworm.com/index.php?rid=2257619&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275669%26dopt%3DAbstract Authors: Hamelin R, Allagnat F, Haefliger JA, Meda P Diabetes and the related metabolic syndrome are multi system disorders that result from improper interactions between various cell types. Even though the underlying mechanism remains to be fully understood, it is most likely that both the long and the short distance range cell interactions, which normally ensure the physiologic functioning of the pancreas, and its relationships with the insulin-targeted organs, are altered. This review focuses on the short-range type of interactions that depend on the contact between adjacent cells and, specifically, on the interactions that are dependent on connexins. The widespread distribution of these membrane proteins, their multiple modes of action, and their interactions with conditions/molecu... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2257619 Sun, 01 Feb 2009 05:00:00 +0100 2257619 http://www.medworm.com/index.php?rid=2257618&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275670%26dopt%3DAbstract Authors: Thomas MK, Tsang SW, Yeung ML, Leung PS, Yao KM PDZ domains are versatile protein interaction modules with the ability to dimerize and to recognize internal and carboxy-terminal peptide motifs. Their function in mediating the formation of multi-molecular signaling complexes is best understood at neuronal and epithelial membranes. In a screen for interactors that regulate transcription factor function in pancreatic beta cells, we isolated two PDZ-containing proteins Bridge-1 (PSMD9) and PDZD2, which contain one and six PDZ domains, respectively. Here, we review their functions in the regulation of pancreatic beta cells as a nuclear coactivator or extracellular signaling molecule. Bridge-1 interacts with both E12 and PDX-1 to stimulate insulin promoter activity. Recent gain-of-f... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2257618 Sun, 01 Feb 2009 05:00:00 +0100 2257618 http://www.medworm.com/index.php?rid=2257617&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275671%26dopt%3DAbstract Authors: Pittenger GL, Taylor-Fishwick D, Vinik AI Efforts to cure diabetes are now focused on restoring a physiologically-regulated population of insulin-producing cells to the patient. A number of animal models of beta cell regeneration have been employed to study the mechanisms of the process. Islet neogenesis, the regeneration of pancreatic islets from pancreatic stem cells, is arguably the least fraught with barriers to widespread use as a therapy for diabetes. These animal models have led to the description of the reg family of proteins that appear to be related to islet regeneration. Islet neogenesis-associated protein (INGAP) is an initiator of islet neogenesis in animal models and a peptide sequence from INGAP carries the biological activity. INGAP peptide has been shown to st... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2257617 Sun, 01 Feb 2009 05:00:00 +0100 2257617 http://www.medworm.com/index.php?rid=2257616&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275672%26dopt%3DAbstract Authors: Knop FK, Vilsbøll T, Holst JJ This review article focuses on the therapeutic potential of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), in treating type 2 diabetes mellitus (T2DM). T2DM is characterized by insulin resistance, impaired glucose-induced insulin secretion and inappropriately regulated glucagon secretion which in combination eventually result in hyperglycemia and in the longer term microvascular and macrovascular diabetic complications. Traditional treatment modalities--even multidrug approaches--for T2DM are often unsatisfactory at getting patients to glycemic goals as the disease progresses due to a steady, relentless decline in pancreatic beta-cell function. Furthermore, current treatment moda... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2257616 Sun, 01 Feb 2009 05:00:00 +0100 2257616 http://www.medworm.com/index.php?rid=2257615&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275673%26dopt%3DAbstract Authors: Scheen AJ Type 2 diabetes is closely related to abdominal obesity and is generally associated with other cardiometabolic risk factors, resulting in a high incidence of cardiovascular complications. Several animal and human observations suggest that the endocannabinoid (EC) system is overactivated in presence of abdominal obesity and/or diabetes, and contributes to disturbances of energy balance and metabolism. Not only it regulates the intake of nutrients through central mechanisms located within the hypothalamus and limbic area, but it also intervenes in transport, metabolism and deposit of the nutrients in the digestive tract, liver, adipose tissue, skeletal muscle, and possibly pancreas. Activation of both central and peripheral CB1 receptors promotes weight gain and associ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2257615 Sun, 01 Feb 2009 05:00:00 +0100 2257615 http://www.medworm.com/index.php?rid=2257614&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275674%26dopt%3DAbstract Authors: Chu KY, Leung PS Angiotensin II (Ang II) is well-known as a systemic vasoconstrictor but recently a novel role for the peptide in endocrine function has been suggested and it has been linked to the pathophysiology of type 2 diabetes mellitus. According to several large-scale clinical studies, blocking Ang II prevented the onset of type 2 diabetes in potential patients. Type 2 diabetes is a complicated disease that is primarily characterized by insulin resistance and relative insulin deficiency mediated by numerous organs. Among these organs, the pancreas, adipose tissue, skeletal muscle and liver are the most prominent in maintaining glucose homeostasis. Interestingly, locally generated Ang II has been identified in these organs, where it plays different physiological roles an... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2257614 Sun, 01 Feb 2009 05:00:00 +0100 2257614 http://www.medworm.com/index.php?rid=2257613&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275675%26dopt%3DAbstract Authors: Atalay M, Oksala N, Lappalainen J, Laaksonen DE, Sen CK, Roy S The heat shock proteins (HSPs), originally identified as heat-inducible gene products, are a highly conserved family of proteins that respond to a wide variety of stress. Although HSPs are among the most abundant intracellular proteins, they are expressed at low levels under normal physiological conditions, and show marked induction in response to various stressors. HSPs function primarily as molecular chaperones, facilitating the folding of other cellular proteins, preventing protein aggregation, or targeting improperly folded proteins to specific pathways for degradation. By modulating inflammation, wound debris clearance, cell proliferation, migration and collagen synthesis, HSPs are essential for normal wound h... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2257613 Sun, 01 Feb 2009 05:00:00 +0100 2257613 http://www.medworm.com/index.php?rid=2257612&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275676%26dopt%3DAbstract Authors: Barnes KM, Miner JL Resistin is a potential link between obesity and insulin resistance or type 2 diabetes. In rodents, resistin is primarily expressed in and secreted from mature adipocytes, with some expression in pancreatic islets and portions of the pituitary and hypothalamus. Its secretion can be up-regulated by several factors, including insulin and glucose. The exposure of rodents, or their cells, to resistin results in decreased response to insulin. This is likely in part due to an up-regulation of suppressor of cytokine signaling (SOCS)-3, which interferes with the activation of insulin receptor substrate (IRS)-1. However, in humans resistin is expressed primarily by macrophages and seems to be involved in the recruitment of other immune cells and the secretion of pro... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2257612 Sun, 01 Feb 2009 05:00:00 +0100 2257612 http://www.medworm.com/index.php?rid=2041666&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075745%26dopt%3DAbstract Authors: Bucki R, Levental I, Kulakowska A, Janmey PA Gelsolin is a highly conserved, multifunctional actin-binding protein initially described in the cytosol of macrophages and subsequently identified in many vertebrate cells. A unique property of gelsolin is that in addition to its widely recognized function as a cytoplasmic regulator of actin organization, the same gene expresses a splice variant coding for a distinct isoform, plasma gelsolin, which is secreted into extracellular fluids. The secreted form of gelsolin has been implicated in a number of processes such as the extracellular actin scavenging system and the presentation of lysophosphatidic acid and other inflammatory mediators to their receptors, in addition to its function as a substrate for extracellular matrix-modulati... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2041666 Mon, 01 Dec 2008 05:00:00 +0100 2041666 http://www.medworm.com/index.php?rid=2041665&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075746%26dopt%3DAbstract Authors: Muga A, Moro F Heat shock proteins (Hsps) are molecular chaperones that oppose stress-induced denaturation of other proteins. Hsps are present in all organisms. Apart from assisting in the efficient folding of newly synthesized proteins they maintain pre-existing proteins in a stable conformation, preventing their aggregation, under stress conditions. The latter role, essential for thermal adaptation, requires that the chaperone system change from a folding to a storing function at heat shock temperatures. The temperature at which this change occurs depends on the presence of a thermosensor in at least one of the components of the chaperone systems. In this review, we focus on the bacterial GroE and DnaK systems, describe their temperature-sensitive protein components, and the... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2041665 Mon, 01 Dec 2008 05:00:00 +0100 2041665 http://www.medworm.com/index.php?rid=2041664&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075747%26dopt%3DAbstract Authors: Cozzetto D, Tramontano A Three dimensional protein structures are crucial for understanding biology at both molecular and system level. Despite the advances in experimental structural biology, the pace of sequence deposition into databanks considerably exceeds that of structure determination. Inevitably the functional annotation of genes and genomes requires the exploitation of bioinformatics methods for protein sequence comparison and structure prediction. Hence monitoring objectively the state of art of the field is of paramount importance, in order to make best use of computational protein models to address biological questions. This review describes some relevant issues in the field of structural bioinformatics, emphasizig both open basic questions and the progress being c... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2041664 Mon, 01 Dec 2008 05:00:00 +0100 2041664 http://www.medworm.com/index.php?rid=2041663&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075748%26dopt%3DAbstract Authors: Verde C, Vergara A, Mazzarella L, di Prisco G Fishes thriving in polar habitats offer many opportunities for comparative approaches to understanding protein adaptations to temperature. Notothenioidei, the dominant suborder in the Antarctic Ocean, have evolved reduction of hemoglobin concentration and multiplicity, perhaps as a consequence of temperature stability and other environmental parameters. In the icefish family, the blood pigment is absent. In contrast, similar to other acanthomorph teleosts, Arctic fish, thriving in a more complex oceanographic system, have maintained higher hemoglobin multiplicity and a highly diversified globin system in response to environmental variability and/or variations in metabolic demands. This review summarises the current knowledge on the... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2041663 Mon, 01 Dec 2008 05:00:00 +0100 2041663 http://www.medworm.com/index.php?rid=2041662&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075749%26dopt%3DAbstract Authors: Matsushima N, Yoshida H, Kumaki Y, Kamiya M, Tanaka T, Izumi Y, Kretsinger RH Tandem repeats occur in 14% of all proteins. The repeat unit lengths range from a single amino acid to more than 100 residues and the repeat number is sometimes over 100. Understanding the structures, functions, and evolution of these repeats is a significant goal in both proteomics and genomics. This review summarizes experimental studies addressing structural features of tandem repeats of short oligopeptides that are rich in proline, glycine, asparagine, serine, and/or threonine. The oligopetides include (PGMG) and (PNN) in biomineralization protein (PM27), and (NPNA) in Plasmodium falciparum circumsporozoite protein, (YSPTSPS) in RNA polymerase II, (PHGGGWGQ) in the prion protein, (YGHGGG(N)) and ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2041662 Mon, 01 Dec 2008 05:00:00 +0100 2041662 http://www.medworm.com/index.php?rid=2041661&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075750%26dopt%3DAbstract Authors: Guo LW, Ruoho AE Intrinsically disordered proteins (IDPs) represent an emerging class of proteins (or domains) that are characterized by a lack of ordered secondary and tertiary structure. This group of proteins has recently attracted tremendous interest primarily because of a unique feature: they can bind to different targets due to their structural plasticity, and thus fulfill diverse functions. The inhibitory gamma-subunit (PDEgamma) of retinal PDE6 is an intriguing IDP, of which unique protein properties are being uncovered. PDEgamma critically regulates the turn on as well as the turn off of visual signaling through alternate interactions with the PDE6 catalytic core, transducin, and the regulator of G protein signaling RGS9-1. The intrinsic disorder of PDEgamma does not ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2041661 Mon, 01 Dec 2008 05:00:00 +0100 2041661 http://www.medworm.com/index.php?rid=2041660&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075751%26dopt%3DAbstract Authors: Barrera FN, Alcaraz LA, Hurtado-Gómez E, Neira JL The first comprehensive studies on the structure and thermodynamics of membrane proteins have started revealing the exact architecture of these macromolecules and the physical-chemical rules behind their structures. In this review, the stabilities of several families of membrane proteins, obtained by using spectroscopic, calorimetric and single molecule techniques are surveyed. The data on the stability of membrane proteins are compared with those obtained in soluble proteins. The comparison indicates that although the number of particular atomic interactions is larger in membrane proteins than in soluble ones, the overall values are similar. The consensus is that some intrinsic properties of membrane proteins resemble tho... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2041660 Mon, 01 Dec 2008 05:00:00 +0100 2041660 http://www.medworm.com/index.php?rid=2041659&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075752%26dopt%3DAbstract Authors: Baccari MC, Bani D The peptide hormone relaxin (RLX) has been shown to exert a variety of functions in both reproductive and non-reproductive tissues. The molecular mechanism of RLX on its target cells appears to involve multiple intracellular signalling systems, including the nitric oxide (NO) pathway. NO is an ubiquitous molecule synthesised from L-arginine under the catalytic action of different nitric oxide synthase (NOS) isoforms and its altered production has been reported to be involved in several diseases. RLX has been demonstrated to promote NO biosynthesis by up-regulating NOS expression; its influence on the different NOS appears to depend on the cell type studied. In addition to its physiological roles, RLX has been postulated as a potential therapeutic agent in se... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=2041659 Mon, 01 Dec 2008 05:00:00 +0100 2041659 http://www.medworm.com/index.php?rid=1880953&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855696%26dopt%3DAbstract Authors: Moors SL, Jonckheer A, De Maeyer M, Engelborghs Y, Ceulemans A We discuss the dynamics of tryptophan rotamers in the context of the non-exponential fluorescence decay in proteins. The central question is: how does the ground-state conformational heterogeneity influence the time evolution of tryptophan fluorescence? This problem is examined here from the theoretical perspective. Three methods at different levels of theory, and with different scopes and computational requirements are reviewed. The Dead-end elimination method is limited to side-chain dynamics and provides an efficient way to detect the stable tryptophan rotamers in a protein. Its application to the study of heterogeneous emission characteristics is illustrated. Molecular dynamics is aimed at the full phase space ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1880953 Wed, 01 Oct 2008 04:00:00 +0100 1880953 http://www.medworm.com/index.php?rid=1880952&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855697%26dopt%3DAbstract Authors: Marasco D, Perretta G, Sabatella M, Ruvo M Combinatorial preparation and HTS of arrays of compounds have increased the speed of drug discovery. A strong impulse in this field has come by the introduction of the solid phase synthesis method that, through automation and miniaturization, has paved the way to the preparation of large collections of compounds in compact and trackable formats. Due to the well established synthetic procedures, peptides have been largely used to develop the basic concepts of combinatorial chemistry and peptide libraries are still successfully employed in screening programs. However, peptides generally do not fulfil the requirements of low conformational flexibility, stability and bioavailability needed for good drug candidates and peptide leads with h... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1880952 Wed, 01 Oct 2008 04:00:00 +0100 1880952 http://www.medworm.com/index.php?rid=1880951&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855698%26dopt%3DAbstract Authors: Pini A, Falciani C, Bracci L The concept of 'magic bullet', initially ascribed to immunoglobulins by Paul Ehrlich at the beginning of the 20th century and strengthened by the hybridoma technology of Kohler and Milstein in the mid 70s, can nowadays be attributed to different target-specific molecules, such as peptides. This attribution is increasingly valid in light of the explosion of new technologies for peptide library construction and screening, not to mention improvements in peptide synthesis and conjugation and in-vivo peptide stability, which make peptide molecules specific bullets for targeting pathological markers and pathogens. Today, hundreds of peptides are being developed and dozens are in clinical trials for a variety of diseases, demonstrating that the general re... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1880951 Wed, 01 Oct 2008 04:00:00 +0100 1880951 http://www.medworm.com/index.php?rid=1880950&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855699%26dopt%3DAbstract Authors: Sanz P Mammalian AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that acts as a sensor of cellular energy status. It is activated by a large variety of cellular stresses that increase cellular AMP and decrease ATP levels and also by physiological stimuli, such as muscle contraction, or by hormones such as leptin and adiponectin. AMPK modulates multiple metabolic pathways. As a result, it has become a target for the development of new drugs for the treatment of type II diabetes, obesity or even cancer. In fact, it has been recently reported that drugs used in the treatment of diabetes, such as metformin and thiazolidinediones (TZDs), exert their beneficial effects through the activation of AMPK. AMPK is a heterotrimeric complex composed of a catalytic s... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1880950 Wed, 01 Oct 2008 04:00:00 +0100 1880950 http://www.medworm.com/index.php?rid=1880949&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855700%26dopt%3DAbstract Authors: Veljkovic N, Glisic S, Prljic J, Perovic V, Botta M, Veljkovic V The field of bioinformatics has become a major part of the drug discovery pipeline playing a key role in improvement and acceleration of this time and money consuming process. Here we review the application of the informational spectrum method (ISM), a virtual spectroscopy method for structure/function analysis of proteins, in identification of functional protein domains representing candidate therapeutic targets for drugs against human immunodeficiency virus (HIV)-1, anthrax, highly pathogenic influenza virus H5N1 and cardiovascular diseases. PMID: 18855700 [PubMed - in process] (Source: Current Protein and Peptide Science) Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1880949 Wed, 01 Oct 2008 04:00:00 +0100 1880949 http://www.medworm.com/index.php?rid=1880948&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18855701%26dopt%3DAbstract Authors: Uversky VN alpha-Synuclein is an abundant presynaptic brain protein, misfolding, aggregation and fibrillation of which are implicated as critical factors in several neurodegenerative diseases. The list of the well-known synucleinopathies includes such devastating disorders as Parkinson's disease, Lewy body variant of Alzheimer's disease, diffuse Lewy body disease, dementia with Lewy bodies, multiple system atrophy, and neurodegeneration with brain iron accumulation type I. The precise functions of alpha-synuclein remain elusive, but there are evidence indicating its involvement in regulation vesicular release and/or turnover and synaptic function in the central nervous system. It might play a role in neuronal plasticity responses, bind fatty acids, regulate certain enzymes, tr... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1880948 Wed, 01 Oct 2008 04:00:00 +0100 1880948 http://www.medworm.com/index.php?rid=1697277&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691122%26dopt%3DAbstract Authors: Shu N, Hovmöller S, Zhou T Different methods for describing and comparing the structures of the tens of thousands of proteins that have been determined by X-ray crystallography are reviewed. Such comparisons are important for understanding the structures and functions of proteins and facilitating structure prediction, as well as assessing structure prediction methods. We summarize methods in this field emphasizing ways of representing protein structures as one-dimensional geometrical strings. Such strings are based on the shape symbols of clustered regions of phi/Psi dihedral angle pairs of the polypeptide backbones as described by the Ramachandran plot. These one-dimensional expressions are as compact as secondary structure description but contain more information in loo... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1697277 Fri, 01 Aug 2008 04:00:00 +0100 1697277 http://www.medworm.com/index.php?rid=1697276&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691123%26dopt%3DAbstract Authors: Dourado DF, Fernandes PA, Ramos MJ Glutathione Transferases (GSTs) are crucial enzymes in the cell detoxification process catalyzing the nucleophilic attack of glutathione (GSH) on toxic electrophilic substrates and producing a less dangerous compound. GSTs studies are of great importance since they have been implicated in the development of drug resistance in tumoral cells and are related to human diseases such as Parkinson's, Alzheimer's, atherosclerois, liver cirrhosis, aging and cataract formation. In this review we start by providing an evolutionary perspective of the mammalian cytosolic GSTs known to date. Later on we focus on the more abundant classes alpha, mu and pi and their structure, catalysis, metabolic associated functions, drug resistance relation and inhibition... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1697276 Fri, 01 Aug 2008 04:00:00 +0100 1697276 http://www.medworm.com/index.php?rid=1697275&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691124%26dopt%3DAbstract Authors: Stepanenko OV, Verkhusha VV, Kuznetsova IC, Uversky VN, Turoverov CK Green fluorescent protein (GFP) from jellyfish Aequorea victoria is the most extensively studied and widely used in cell biology protein. GFP-like proteins constitute a fast growing family as several naturally occurring GFP-like proteins have been discovered and enhanced mutants of Aequorea GFP have been created. These mutants differ from wild-type GFP by conformational stability, quantum yield, spectroscopic properties (positions of absorption and fluorescence spectra) and by photochemical properties. GFP-like proteins are very diverse, as they can be not only green, but also blue, orange-red, far-red, cyan, and yellow. They also can have dual-color fluorescence (e.g., green and red) or be non-fluorescent. S... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1697275 Fri, 01 Aug 2008 04:00:00 +0100 1697275 http://www.medworm.com/index.php?rid=1697274&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691125%26dopt%3DAbstract Authors: Benito A, Laurents DV, Ribó M, Vilanova M Pancreatic-type ribonucleases are a family of RNA degrading enzymes that share different degrees of sequence identity but a very similar 3D-structure. The prototype of this family is bovine pancreatic ribonuclease or ribonuclease A. This enzyme has been the object of landmark work on the folding, stability, protein chemistry, catalysis, enzyme-substrate interaction and molecular evolution. In the recent years, the interest in the study of pancreatic-type ribonucleases has increased due to the involvement of some members of this family in special biological functions. In addition, dimeric and also higher oligomeric structures can be attained by the members of this family. The oligomers described structurally to date are mainly form... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1697274 Fri, 01 Aug 2008 04:00:00 +0100 1697274 http://www.medworm.com/index.php?rid=1697273&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691126%26dopt%3DAbstract Authors: de Vries SJ, Bonvin AM Protein-protein interface prediction is a booming field, with a substantial growth in the number of new methods being published the last two years. The increasing number of available three-dimensional structures of protein-protein complexes has enabled large-scale statistical analyses of protein interfaces, considering evolutionary, physicochemical and structural properties. Successful combinations of these properties have led to more accurate interface predictors in recent years. In addition to parametric combination, machine learning algorithms have become popular. In the meantime, assessing the absolute and relative performance of interface predictors remains very difficult: This is due to differences in both the output of the various interface predic... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1697273 Fri, 01 Aug 2008 04:00:00 +0100 1697273 http://www.medworm.com/index.php?rid=1697272&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691127%26dopt%3DAbstract Authors: Roccatano D Pure organic solvents or mixtures with water are very common environments for studying protein and peptide in solution. These milieu conditions are used either for improving the catalytic performance of enzymes or for studying the effect of solvent on the protein stability and hence gaining insight into the protein folding mechanism. The atomic details of these processes are mainly addressed using computer simulation approaches. In particular, Molecular Dynamics simulation represents the most powerful and versatile tool to investigate the details of solvation processes at atomic level. In the last few years, the number of publications peptide and protein simulations in non-natural environments has proliferated. These studies are providing important contributions to... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1697272 Fri, 01 Aug 2008 04:00:00 +0100 1697272 http://www.medworm.com/index.php?rid=1566651&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18537676%26dopt%3DAbstract Authors: Belizario JE, Alves J, Garay-Malpartida M, Occhiucci JM The degradation is critical to activation and deactivation of regulatory proteins involved in signaling pathways to cell growth, differentiation, stress responses and physiological cell death. Proteins carry domains and sequence motifs that function as prerequisite for their proteolysis by either individual proteases or the 26S multicomplex proteasomes. Two models for entry of substrates into the proteasomes have been considered. In one model, it is proposed that the ubiquitin chain attached to the protein serves as recognition element to drag them into the 19S regulatory particle, which promotes the unfolding required to its access into the 20S catalytic chamber. In second model, it is proposed that an unstructured tail ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566651 Sun, 01 Jun 2008 04:00:00 +0100 1566651 http://www.medworm.com/index.php?rid=1566650&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18537677%26dopt%3DAbstract Authors: Stoll R, Bosserhoff A In the year 1994, the protein MIA (melanoma inhibitory activity) was found to be strongly expressed and secreted by malignant melanomas and subsequent studies revealed that MIA has an important function in melanoma development and invasion. Multidimensional NMR-spectroscopy and x-ray crystallography revealed that recombinant human MIA adopts a Src homology 3 (SH3) domain-like fold in solution, a structure with two perpendicular antiparallel three- and five-stranded beta-sheets. SH3 domains are protein modules that are found in many intracellular signalling proteins and mediate protein-protein interactions by binding to proline-rich peptide sequences. Unlike previously described protein structures with SH3 domain folds, MIA is a secreted single-domain prot... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566650 Sun, 01 Jun 2008 04:00:00 +0100 1566650 http://www.medworm.com/index.php?rid=1566649&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18537678%26dopt%3DAbstract Authors: Yang H, Landis-Piwowar KR, Chen D, Milacic V, Dou QP The proteasome is a multicatalytic protease complex that degrades most endogenous proteins including misfolded or damaged proteins to ensure normal cellular function. The ubiquitin-proteasome degradation pathway plays an essential role in multiple cellular processes, including cell cycle progression, proliferation, apoptosis and angiogenesis. It has been shown that human cancer cells are more sensitive to proteasome inhibition than normal cells, indicating that a proteasome inhibitor could be used as a novel anticancer drug. Indeed, this idea has been supported by the encouraging results of the clinical trials using the proteasome inhibitor Bortezomib (Velcade, PS-341), a drug approved by the US Food and Drug Administration ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566649 Sun, 01 Jun 2008 04:00:00 +0100 1566649 http://www.medworm.com/index.php?rid=1566648&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18537679%26dopt%3DAbstract Authors: Fry DC Protein-protein interactions represent targets for drug discovery that are highly relevant in a biological sense, but have proven difficult in a practical sense. Nevertheless, there have been recent successes in discovering drug-like small molecule inhibitors of protein-protein systems. To build on this progress, it is worth analyzing successful cases to understand at a molecular level the strategies by which these compounds effectively interfere with protein-protein pairing. A commonly observed situation is one wherein the small molecule acts as a direct mimic of one of the protein partners. This review focuses exclusively on cases where this strategy is employed, and examines the structural characteristics of the binding sites and the conformational attributes of the ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566648 Sun, 01 Jun 2008 04:00:00 +0100 1566648 http://www.medworm.com/index.php?rid=1566647&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18537680%26dopt%3DAbstract Authors: Du QS, Huang RB, Chou KC This review is to summarize three new QSAR (quantitative structure-activity relationship) methods recently developed in our group and their applications for drug design. Based on more solid theoretical models and advanced mathematical techniques, the conventional QSAR technique has been recast in the following three aspects. (1) In the fragment-based two dimensional QSAR, or abbreviated as FB-QSAR, the molecular structures in a family of drug candidates are divided into several fragments according to the substitutes being investigated. The bioactivities of drug candidates are correlated with physicochemical properties of the molecular fragments through two sets of coefficients: one is for the physicochemical properties and the other for the molecular f... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566647 Sun, 01 Jun 2008 04:00:00 +0100 1566647 http://www.medworm.com/index.php?rid=1566646&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18537681%26dopt%3DAbstract Authors: Oakley MT, Barthel D, Bykov Y, Garibaldi JM, Burke EK, Krasnogor N, Hirst JD Optimisation problems pervade structural bioinformatics. In this review, we describe recent work addressing a selection of bioinformatics challenges. We begin with a discussion of research into protein structure comparison, and highlight the utility of Kolmogorov complexity as a measure of structural similarity. We then turn to research into de novo protein structure prediction, in which structures are generated from first principles. In this endeavour, there is a compromise between the detail of the model and the extent to which the conformational space of the protein can be sampled. We discuss some developments in this area, including off-lattice structure prediction using the great deluge algorithm... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566646 Sun, 01 Jun 2008 04:00:00 +0100 1566646 http://www.medworm.com/index.php?rid=1566645&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18537682%26dopt%3DAbstract The objective of this review is to elucidate its origin and elementary structure, and to discuss its structure basis of activity and action mechanisms based on the latest research. Furthermore, some published studies reporting the antiangiogenic effects of endostatin-derived peptides were also reviewed. It is proposed that the amino acid sequence of endostatin contains both angiosuppressive and angiostimulatory domains. Short endostatin fragments may be exploited as a new angiogenesis inhibitor for therapeutic applications, in substitution of the full length endostatin. These studies on endostatin fragments also shed light on our understanding of the molecular action mechanisms of endostatin. PMID: 18537682 [PubMed - in process] (Source: Current Protein and Peptide Science) Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566645 Sun, 01 Jun 2008 04:00:00 +0100 1566645 http://www.medworm.com/index.php?rid=1566644&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18537683%26dopt%3DAbstract Authors: Sau S, Chattoraj P, Ganguly T, Chanda PK, Mandal NC Bacteriophages utilize host bacterial cellular machineries for their own reproduction and completion of life cycles. The early proteins that phage synthesize immediately after the entry of their genomes into bacterial cells participate in inhibiting host macromolecular biosynthesis, initiating phage-specific replication and synthesizing late proteins. Inhibition of synthesis of host macromolecules that eventually leads to cell death is generally performed by the physical and/or chemical modification of indispensable host proteins by early proteins. Interestingly, most modified bacterial proteins were shown to take part actively in phage-specific transcription and replication. Research on phages in last nine decades has demons... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566644 Sun, 01 Jun 2008 04:00:00 +0100 1566644 http://www.medworm.com/index.php?rid=1566643&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18537684%26dopt%3DAbstract Authors: Iconomidou VA, Hamodrakas SJ Amyloidoses are a group of diseases including neurodegenerative diseases like Alzheimer's disease and also type II diabetes, spongiform encephalopathies and many others, believed to be caused by protein aggregation and subsequent amyloid fibril formation. However, occasionally, living organisms exploit amyloid fibril formation, a property inherent into amino acid sequences, and perform specific physiological functions from amyloids, in differing biological contexts. Some of these functional amyloids are natural protective amyloids. Here, we review recent evidence on silkmoth chorion protein synthetic peptide-analogues that documents the function of silkmoth chorion, the major component of the eggshell, a structure with extraordinary physiological a... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566643 Sun, 01 Jun 2008 04:00:00 +0100 1566643 http://www.medworm.com/index.php?rid=1566657&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18393883%26dopt%3DAbstract Authors: Mehta A, Magalhães BS, Souza DS, Vasconcelos EA, Silva LP, Grossi-de-Sa MF, Franco OL, da Costa PH, Rocha TL In recent years, a strong emphasis has been given in deciphering the function of genes unraveled by the completion of several genome sequencing projects. In plants, functional genomics has been massively used in order to search for gene products of agronomic relevance. As far as root-pathogen interactions are concerned, several genes are recognized to provide tolerance/resistance against potential invaders. However, very few proteins have been identified by using current proteomic approaches. One of the major drawbacks for the successful analysis of root proteomes is the inherent characteristics of this tissue, which include low volume content and high concentratio... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566657 Tue, 01 Apr 2008 04:00:00 +0100 1566657 http://www.medworm.com/index.php?rid=1566656&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18393884%26dopt%3DAbstract Authors: de Ruyck J, Wouters J Biosynthesis of the universal terpenoid precursors, isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), from three acetyl CoA moieties through mevalonate was studied extensively in the 1950s. For several decades, the mevalonate paradigm reigned supreme and a mevalonate origin was attributed to a growing number of natural products, in many cases erroneously. Besides this biosynthetic pathway, the existence of a second one leading to IPP and DMAPP through 1-deoxy-D-xylulose 5-phosphate and 2C-methyl-D-erythritol 4-phosphate was discovered more recently in plants and some eubacteria. This pathway is widely distributed in the bacterial kingdom including major human pathogens, such as Mycobacterium tuberculosis or Helicobacter pylori and is al... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566656 Tue, 01 Apr 2008 04:00:00 +0100 1566656 http://www.medworm.com/index.php?rid=1566655&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18393885%26dopt%3DAbstract Authors: Mansell TJ, Fisher AC, DeLisa MP Gram-negative bacteria, especially Escherichia coli, are often the preferred hosts for recombinant protein production because of their fast doubling times, ability to grow to high cell density, propensity for high recombinant protein titers and straightforward protein purification techniques. The utility of simple bacteria in such studies continues to improve as a result of an ever-increasing body of knowledge regarding their native protein biogenesis machinery. From translation on the ribosome to interaction with cytosolic accessory factors to transport across the inner membrane into the periplasmic space, cellular proteins interact with many different types of cellular machinery and each interaction can have a profound effect on the protein f... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566655 Tue, 01 Apr 2008 04:00:00 +0100 1566655 http://www.medworm.com/index.php?rid=1566654&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18393886%26dopt%3DAbstract Authors: Bruneaux M, Rousselot M, Leize E, Lallier FH, Zal F Understanding the function of macromolecular complexes is related to a precise knowledge of their structure. These large complexes are often fragile high molecular mass noncovalent multimeric proteins. Classical biochemical methods for determination of their native mass and subunit composition were used to resolve their quaternary structure, sometimes leading to different models. Recently, the development of mass spectrometry and multi-angle laser light scattering (MALLS) has enabled absolute determination of native masses and subunit masses. Electrospray ionization mass spectrometry (ESI-MS) was used in denaturing and native conditions to probe subunit composition and noncovalent assemblies masses up to 2.25 MDa. In a comple... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566654 Tue, 01 Apr 2008 04:00:00 +0100 1566654 http://www.medworm.com/index.php?rid=1566653&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18393887%26dopt%3DAbstract Authors: Morra G, Meli M, Colombo G Computer simulations of proteins, lipids and nucleic acids at equilibrium have become essentially routine. However, the fact remains that complete sampling of conformational space continues to be a bottle-neck in the field. The challenge for the future is to overcome such problems and use computational approaches to understand recognition and spontaneous self-organization in biomolecular systems (folding, aggregation and assembly of complexes), processes that cannot be directly observed experimentally. In this review, examples illustrating the extent to which simulations can be used to understand these phenomena in biomolecular systems will be presented along with examples of methodological developments to increase our physical understanding of the p... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566653 Tue, 01 Apr 2008 04:00:00 +0100 1566653 http://www.medworm.com/index.php?rid=1566652&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18393888%26dopt%3DAbstract Authors: Kümmel D, Heinemann U The term 'tethering factor' has been coined for a heterogeneous group of proteins that all are required for protein trafficking prior to vesicle docking and SNARE-mediated membrane fusion. Two groups of tethering factors can be distinguished, long coiled-coil proteins and multi-subunit complexes. To date, eight such protein complexes have been identified in yeast, and they are required for different trafficking steps. Homologous complexes are found in all eukaryotic organisms, but conservation seems to be less strict than for other components of the trafficking machinery. In fact, for most proposed multi-subunit tethers their ability to actually bridge two membranes remains to be shown. Here we discuss recent progress in the structural and functional... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566652 Tue, 01 Apr 2008 04:00:00 +0100 1566652 http://www.medworm.com/index.php?rid=1566664&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18336319%26dopt%3DAbstract This article gives an overview of recent progress in protein-protein docking and it identifies several directions for future research. Recent results from the CAPRI blind docking experiments show that docking algorithms are steadily improving in both reliability and accuracy. Current docking algorithms employ a range of efficient search and scoring strategies, including e.g. fast Fourier transform correlations, geometric hashing, and Monte Carlo techniques. These approaches can often produce a relatively small list of up to a few thousand orientations, amongst which a near-native binding mode is often observed. However, despite the use of improved scoring functions which typically include models of desolvation, hydrophobicity, and electrostatics, current algorithms still have difficulty in... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566664 Fri, 01 Feb 2008 05:00:00 +0100 1566664 http://www.medworm.com/index.php?rid=1566663&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18336320%26dopt%3DAbstract Authors: Banerjee M, Johnson JE Host cell entry by influenza and other enveloped viruses is well characterized, however, the manner in which non-enveloped viruses deliver their genome across host cell membranes in the absence of membrane fusion remains unresolved. The discovery of short, membrane altering, amphipathic or hydrophobic sequences in several non-enveloped virus capsid proteins such as the gamma (gamma) peptide of nodaviruses and tetraviruses, VP4 and the N-terminal region of VP1 of picornaviruses, micro1N of reoviruses, and protein VI of adenoviruses suggests that these small peptides facilitate breaching of the host membrane and the delivery of the viral genome into the host cell. In spite of conspicuous differences in entry among non-enveloped virions, the short stretches... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566663 Fri, 01 Feb 2008 05:00:00 +0100 1566663 http://www.medworm.com/index.php?rid=1566662&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18336321%26dopt%3DAbstract Authors: Krishnan A, Zbilut JP, Tomita M, Giuliani A The network paradigm is based on the derivation of emerging properties of studied systems by their representation as oriented graphs: any system is traced back to a set of nodes (its constituent elements) linked by edges (arcs) correspondent to the relations existing between the nodes. This allows for a straightforward quantitative formalization of systems by means of the computation of mathematical descriptors of such graphs (graph theory). The network paradigm is particularly useful when it is clear which elements of the modelled system must play the role of nodes and arcs respectively, and when topological constraints have a major role with respect to kinetic ones. In this review we demonstrate how nodes and arcs of protein topolo... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566662 Fri, 01 Feb 2008 05:00:00 +0100 1566662 http://www.medworm.com/index.php?rid=1566661&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18336322%26dopt%3DAbstract Authors: Draper LA, Ross RP, Hill C, Cotter PD Lantibiotics are a diverse family of bacterially synthesized antimicrobial peptides produced by gram-positive bacteria. They usually have a broad spectrum of targets, often including closely related strains. The production of lantibiotics must thus be coupled with a mechanism by which the producing strain can protect itself from the lethal action of its own antimicrobial compound. This mechanism is referred to as immunity. Lantibiotic immunity is usually provided by one, or both, of two methods i.e. by a specific immunity peptide (designated LanI) and/or a specialised ABC transporter system (designated LanFE(G)). Significantly, although the specific immunity peptides function in a similar manner, there is very little homology between them.... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566661 Fri, 01 Feb 2008 05:00:00 +0100 1566661 http://www.medworm.com/index.php?rid=1566660&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18336323%26dopt%3DAbstract Authors: Wang G In living cells, membrane proteins are essential to signal transduction, nutrient use, and energy exchange between the cell and environment. Due to challenges in protein expression, purification and crystallization, deposition of membrane protein structures in the Protein Data Bank lags far behind existing structures for soluble proteins. This review describes recent advances in solution NMR allowing the study of a select set of peripheral and integral membrane proteins. Surface-binding proteins discussed include amphitropic proteins, antimicrobial and anticancer peptides, the HIV-1 gp41 peptides, human alpha-synuclein and apolipoproteins. Also discussed are transmembrane proteins including bacterial outer membrane beta-barrel proteins and oligomeric alpha-helical prote... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566660 Fri, 01 Feb 2008 05:00:00 +0100 1566660 http://www.medworm.com/index.php?rid=1566659&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18336324%26dopt%3DAbstract This article evaluates the strategies, current progresses, reported prediction performances, available software tools, and underlying difficulties in using SVM for predicting the functional class of proteins and peptides. PMID: 18336324 [PubMed - indexed for MEDLINE] (Source: Current Protein and Peptide Science) Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566659 Fri, 01 Feb 2008 05:00:00 +0100 1566659 http://www.medworm.com/index.php?rid=1566658&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18336325%26dopt%3DAbstract Authors: Szeltner Z, Polgár L A group of serine peptidases, the prolyl oligopeptidase family, cannot hydrolyze proteins and peptides containing more than 30 residues. The crystal structure of prolyl oligopeptidase (POP) has shown that the enzyme is composed of a peptidase domain with an alpha/beta hydrolase fold and a seven-bladed beta-propeller domain. This domain covers the catalytic triad and excludes large, structured peptides from the active site. The mechanism of substrate selection has been reviewed, along with the binding mode of the substrate and the catalytic mechanism, which differ from that of the classical serine peptidases in several features. POP is essentially a cytosolic enzyme and has been shown to be involved in a number of biological processes, but its precise ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566658 Fri, 01 Feb 2008 05:00:00 +0100 1566658 http://www.medworm.com/index.php?rid=1566671&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220841%26dopt%3DAbstract Authors: Finkelstein AV, Ivankov DN, Garbuzynskiy SO, Galzitskaya OV The first part of this paper contains an overview of protein structures, their spontaneous formation ("folding"), and the thermodynamic and kinetic aspects of this phenomenon, as revealed by in vitro experiments. It is stressed that universal features of folding are observed near the point of thermodynamic equilibrium between the native and denatured states of the protein. Here the "two-state" ("denatured state" <--> "native state") transition proceeds without accumulation of metastable intermediates, but includes only the unstable "transition state". This state, which is the most unstable in the folding pathway, and its structured core (a "nucleus") are distinguished by their essential influence on the folding/... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566671 Sat, 01 Dec 2007 05:00:00 +0100 1566671 http://www.medworm.com/index.php?rid=1566670&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220842%26dopt%3DAbstract Authors: Trexler AJ, Nilsson MR Amyloid fibrils are highly ordered protein assemblies known to contribute to the pathology of a variety of genetic and aging-associated diseases. More recently, these fibrils have been shown to be useful as structural scaffolds in both natural biological systems and nanotechnology applications. The intense interest in amyloid fibrils has led to the investigation of well-characterized proteins, such as hen egg white lysozyme (HEWL), as model systems to examine structural and mechanistic principles that may be generally applicable to all amyloid fibrils. The purpose of this review is to critically examine the fibril-formation literature of proteins in the lysozyme family with respect to the known structure and folding properties of these proteins. The goal... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566670 Sat, 01 Dec 2007 05:00:00 +0100 1566670 http://www.medworm.com/index.php?rid=1566669&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220843%26dopt%3DAbstract Authors: Alegre-Cebollada J, Oñaderra M, Gavilanes JG, del Pozo AM Actinoporins are a family of 20-kDa, basic proteins isolated from sea anemones, whose activity is inhibited by preincubation with sphingomyelin. They are produced in monomeric soluble form but, when binding to the plasma membrane, they oligomerize to produce functional pores which result in cell lysis. Equinatoxin II (EqtII) from Actinia equina and Sticholysin II (StnII) from Stichodactyla helianthus are the actinoporins that have been studied in more detail. Both proteins display a beta-sandwich fold composed of 10 beta-strands flanked on each side by two short alpha-helices. Two-dimensional crystallization on lipid monolayers has allowed the determination of low-resolution models of tetrameric structures distinct... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566669 Sat, 01 Dec 2007 05:00:00 +0100 1566669 http://www.medworm.com/index.php?rid=1566668&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220844%26dopt%3DAbstract Authors: Khare SD, Dokholyan NV Protein aggregation is implicated in a plethora of neurodegenerative diseases. The proteins found to aggregate in these diseases are unrelated in their native structures and amino acid sequences, but form similar insoluble fibrils with characteristic cross-beta sheet morphologies called amyloid in the aggregated state. While both the mechanism of aggregation and the structure of the aggregates are not fully understood at the molecular level, recent studies provide strong support for the idea that protein aggregation into highly stable, insoluble amyloid structures is a general property of the polypeptide chain. For proteins with a unique native state, it is known that aggregation occurs under conditions that promote native-state destabilization in vitro ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566668 Sat, 01 Dec 2007 05:00:00 +0100 1566668 http://www.medworm.com/index.php?rid=1566667&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220845%26dopt%3DAbstract Authors: Gromiha MM, Suwa M beta-barrel membrane proteins perform a variety of functions, such as mediating non-specific, passive transport of ions and small molecules, selectively passing the molecules like maltose and sucrose and are involved in voltage dependent anion channels. Understanding the structural features of beta-barrel membrane proteins and detecting them in genomic sequences are challenging tasks in structural and functional genomics. In this review, with the survey of experimentally known amino acid sequences and structures, the characteristic features of amino acid residues in beta-barrel membrane proteins and novel parameters for understanding their folding and stability will be described. The development of statistical methods and machine learning techniques for disc... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566667 Sat, 01 Dec 2007 05:00:00 +0100 1566667 http://www.medworm.com/index.php?rid=1566666&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220846%26dopt%3DAbstract Authors: Pollegioni L, Sacchi S, Caldinelli L, Boselli A, Pilone MS, Piubelli L, Molla G D-amino acid oxidase (DAAO) is a FAD-containing flavoprotein that dehydrogenates the D-isomer of amino acids to the corresponding imino acids, coupled with the reduction of FAD. The cofactor then reoxidizes on molecular oxygen and the imino acid hydrolyzes spontaneously to the alpha-keto acid and ammonia. In vitro DAAO displays broad substrate specificity, acting on several neutral and basic D-amino acids: the most efficient substrates are amino acids with hydrophobic side chains. D-aspartic acid and D-glutamic acid are not substrates for DAAO. Through the years, it has been the subject of a number of structural, functional and kinetic investigations. The most recent advances are represented by sit... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566666 Sat, 01 Dec 2007 05:00:00 +0100 1566666 http://www.medworm.com/index.php?rid=1566665&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18220847%26dopt%3DAbstract Authors: Jana S, Paliwal J The human liver cytochromes P450 (CYP P450s) are superfamily of hemoproteins responsible for catalyzing the oxidative metabolism of drugs and xenobiotics entering human body. Drug-drug/xenobiotic interactions are a major cause of therapeutic failures and adverse events. The concomitant administration of inducers with other drugs that are metabolized by CYP450 can result in their altered metabolism in the gastrointestinal tract and/ or liver. The clinical importance of such interactions includes auto induction leading to suboptimal or failed treatment. It is a major concern for the drug companies while developing new drugs. The present understanding of the mechanisms of induction of CYP P450s enzymes and their regulation has made considerable progress during l... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566665 Sat, 01 Dec 2007 05:00:00 +0100 1566665 http://www.medworm.com/index.php?rid=1566680&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17979757%26dopt%3DAbstract Authors: Krishna KA, Rao GV, Rao KR The structure of Escherichia coli chaperonin GroEL was studied using various experimental tools. Such studies produced information about its structure with increasing details. Moreover, remarkable advances in experimental methods provided a step forward in understanding the reaction cycle involved in GroEL-mediated protein folding. In the current review we summarize recent progress, focus on the structure of GroEL and understand the mechanism involved in GroEL-mediated protein folding. This review is divided into the following sections: (i) Section 1 provides basic understanding on protein folding, (ii) Section 2 not only describes various tools used to elucidate the structural aspects of GroEL but also provides details about its structure with parti... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566680 Mon, 01 Oct 2007 04:00:00 +0100 1566680 http://www.medworm.com/index.php?rid=1566679&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17979758%26dopt%3DAbstract Authors: von Braun SS, Schleiff E Mitochondria and chloroplasts are both of endosymbiotic origin. Upon symbiosis the ancestral bacteria had to be incorporated into the regulatory cellular network. A long known phenomenon is thereby the alteration of the positioning of the organelles in response to extra- and intracellular stimuli. For chloroplasts, the repositioning is a response to light intensity changes in order to optimize the photosynthetic process. Mitochondria movement ensures a positioning of the organelle close to the place where its function is required, e.g. in metabolic pathways, apoptosis, regulation of cytosolic calcium levels and ATP production. Even though the morphological description of the movement was circumstantiated decades ago, only recent research gave some insi... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566679 Mon, 01 Oct 2007 04:00:00 +0100 1566679 http://www.medworm.com/index.php?rid=1566678&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17979759%26dopt%3DAbstract Authors: Fox T, Brennan D, Austen DA, Swalley SE, Coll JT, Raybuck SA, Chambers SP Structure-based drug design (SBDD) has played an integral role in the development of highly specific, potent protease inhibitors resulting in a number of drugs in clinical trials and on the market. Possessing biochemical assays and structural information on both the target protease and homologous family members helps ensure compound selectivity. We have redesigned the path from clone to protein eliminating many of the traditional bottlenecks associated with protein production to ensure a constant supply to feed many diverse protease drug discovery programs. The process was initiated with the design of a multi-system vector, capable of expression in both eukaryotic and prokaryotic hosts; this vector also ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566678 Mon, 01 Oct 2007 04:00:00 +0100 1566678 http://www.medworm.com/index.php?rid=1566677&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17979760%26dopt%3DAbstract Authors: Wong JH, Xia L, Ng TB Defensins are a family of peptides with potent antimicrobial activity. They are found in various organisms. The intent of this article is to review the structures and mechanisms of antimicrobial actions of defensins produced by different organisms including humans, other mammals, birds, reptiles, fish, mollusks, arthropods, plants and fungi. The evolution and possible applications of these defensins are discussed. PMID: 17979760 [PubMed - indexed for MEDLINE] (Source: Current Protein and Peptide Science) Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566677 Mon, 01 Oct 2007 04:00:00 +0100 1566677 http://www.medworm.com/index.php?rid=1566676&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17979761%26dopt%3DAbstract Authors: Agnati LF, Guidolin D, Leo G, Genedani S, Arhem P, Forni A, Andreoli N, Fuxe K Biological systems are organized in intricate and highly structured networks with hierarchies and multiple scales. Cells can be considered as "meso-scale level" systems placed between the "macro-scale level" (systems of cellular networks) and the "micro-scale level" (systems of molecular networks). In fact, cells represent complex biochemical machineries made by networks of molecules connected by biochemical reactions. Thus, the brain should be studied as a system of "networks of networks". Recently, the existence of a Global Molecular Network (GMN) enmeshing the entire CNS was proposed. This proposal is based on the evidence that the extra-cellular matrix is a dynamic molecular structure capable of... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566676 Mon, 01 Oct 2007 04:00:00 +0100 1566676 http://www.medworm.com/index.php?rid=1566675&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17979762%26dopt%3DAbstract Authors: Sebestík J, Hlavácek J, Stibor I The 9-aminoacridines play an important role in medicine. They were applied first in a treatment of protozoal infections in the beginning of the last century. Recently, it has been shown that the 9-aminoacridines are successful candidates for treatment of cancer, viral and prion diseases. Their conjugation with biomolecules such as peptides and proteins may modulate their activity, bioavailability and applicability. This review deals with the synthesis of 9-aminoacridine, its conjugation with variety of molecules and utilization of such conjugates in several fields of science. PMID: 17979762 [PubMed - indexed for MEDLINE] (Source: Current Protein and Peptide Science) Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566675 Mon, 01 Oct 2007 04:00:00 +0100 1566675 http://www.medworm.com/index.php?rid=1566674&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17979763%26dopt%3DAbstract Authors: Wouters MA, George RA, Haworth NL Seminal studies by Richardson and Thornton defined the constraints imposed by protein structure on disulfide formation and flagged forbidden regions of primary or secondary structure seemingly incapable of forming disulfide bonds between resident cysteine pairs. With respect to secondary structure, disulfide bonds were not found between cysteine pairs: A. on adjacent beta-stands; B. in a single helix or strand; C. on non-adjacent strands of the same beta-sheet. In primary structure, disulfide bonds were not found between cysteine pairs: D. adjacent in the sequence. In the intervening years it has become apparent that all these forbidden regions are indeed occupied by disulfide-bonded cysteines, albeit rather strained ones. It has been observed... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566674 Mon, 01 Oct 2007 04:00:00 +0100 1566674 http://www.medworm.com/index.php?rid=1566673&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17979764%26dopt%3DAbstract Authors: Ahn T, Kim M, Yun CH, Chae HJ Knowledge regarding the regulation of hepatic cytochrome P450 (P450) is crucial to the fields of drug therapy and drug development, as well as to our understanding of the mechanisms underlying the metabolic activation of toxic and carcinogenic compounds. P450 is a membrane-anchored protein that shows a variety of interaction with membrane phospholipids, which affect the membrane topology and catalytic activities of the protein. In particular, anionic phospholipids, nonbilayer forming lipids, and the degree of saturation of the lipid fatty acyl chain play important roles in the functional regulation of P450, as well as in the bilayer structure of the membrane. However, despite the importance of phospholipids in the regulation of P450s, the interact... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566673 Mon, 01 Oct 2007 04:00:00 +0100 1566673 http://www.medworm.com/index.php?rid=1566672&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17979765%26dopt%3DAbstract This article is a comprehensive review on the role of antimicrobial peptides in burns and wounds. PMID: 17979765 [PubMed - indexed for MEDLINE] (Source: Current Protein and Peptide Science) Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566672 Mon, 01 Oct 2007 04:00:00 +0100 1566672 http://www.medworm.com/index.php?rid=1566687&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17696866%26dopt%3DAbstract Authors: Kroemer RT This review gives an introduction into ligand - receptor docking and illustrates the basic underlying concepts. An overview of different approaches and algorithms is provided. Although the application of docking and scoring has led to some remarkable successes, there are still some major challenges ahead, which are outlined here as well. Approaches to address some of these challenges and the latest developments in the area are presented. Some aspects of the assessment of docking program performance are discussed. A number of successful applications of structure-based virtual screening are described. PMID: 17696866 [PubMed - indexed for MEDLINE] (Source: Current Protein and Peptide Science) Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566687 Wed, 01 Aug 2007 04:00:00 +0100 1566687 http://www.medworm.com/index.php?rid=1566686&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17696867%26dopt%3DAbstract Authors: Reddy AS, Pati SP, Kumar PP, Pradeep HN, Sastry GN Virtual screening emerged as an important tool in our quest to access novel drug like compounds. There are a wide range of comparable and contrasting methodological protocols available in screening databases for the lead compounds. The number of methods and software packages which employ the target and ligand based virtual screening are increasing at a rapid pace. However, the general understanding on the applicability and limitations of these methodologies is not emerging as fast as the developments of various methods. Therefore, it is extremely important to compare and contrast various protocols with practical examples to gauge the strength and applicability of various methods. The review provides a comprehensive appraisal o... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566686 Wed, 01 Aug 2007 04:00:00 +0100 1566686 http://www.medworm.com/index.php?rid=1566685&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17696868%26dopt%3DAbstract Authors: Patel DS, Dessalew N, Iqbal P, Bharatam PV Glycogen Synthase Kinase-3 (GSK-3) is a serine/threonine kinase with varied number of actions in cellular signalling systems making it an emerging target for diseases such as diabetes mellitus, cancer, chronic inflammation, bipolar affective disorders and Alzheimer's disease. Various efforts have produced many potent small molecule inhibitors of GSK-3, which are being tested for modulation of glycogen metabolism, gene transcription, apoptosis and enhancement of insulin-stimulated glucose transport. Majority of the reported inhibitors show their inhibitory effects towards other phylogenetically related kinases also, like cyclin dependant kinases (CDKs). Thus it is important to develop inhibitors that can inhibit GSK-3 selectively. Rati... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566685 Wed, 01 Aug 2007 04:00:00 +0100 1566685 http://www.medworm.com/index.php?rid=1566684&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17696869%26dopt%3DAbstract Authors: Holton SJ, Weiss MS, Tucker PA, Wilmanns M Tuberculosis has become one of the deadliest global emergencies due to the widespread existence of multiple drug resistance strains of Mycobacterium tuberculosis and the increase of immuno-compromised populations in large parts of the world. Although the complete genome of M. tuberculosis became available in 1998, opening unprecedented opportunities for target-specific drug development, the progress since then has been slow, mainly due to a lack of a sufficiently strong interest by pharmaceutical and biotechnology industries. One of the most promising tools for future drug discovery lies in the elucidation of the molecular structures of potential drug targets from the M. tuberculosis proteome. During the last five years, the structure... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566684 Wed, 01 Aug 2007 04:00:00 +0100 1566684 http://www.medworm.com/index.php?rid=1566683&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17696870%26dopt%3DAbstract Authors: Kishan KV Structure based drug designing is now a popular technique used for increasing the speed of drug designing process. This was made possible by the availability of many protein structures which helped in developing tools to understand the structure function relationships, automated docking and virtual screening. Knowledge of structure based functional properties of a drug target is very essential for a successful in silico designing of drugs. However, some problems associated with the structure determination process and lack of knowledge of conformational freedom associated with available protein structures are the hurdles involved in structure based drug designing. Docking and virtual screening processes depend on the active site structure of the receptor molecule and ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566683 Wed, 01 Aug 2007 04:00:00 +0100 1566683 http://www.medworm.com/index.php?rid=1566682&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17696871%26dopt%3DAbstract Authors: Villoutreix BO, Renault N, Lagorce D, Sperandio O, Montes M, Miteva MA In today's research environment, a wealth of experimental/theoretical structural data is available and the number of therapeutically relevant macromolecular structures is growing rapidly. This, coupled with the huge number of small non-peptide potential drug candidates easily available (over 7 million compounds), highlight the need of using computer-aided techniques for the efficient identification and optimization of novel hit compounds. Virtual (or in silico) ligand screening based on the three-dimensional structure of macromolecular targets (SB-VLS) is firmly established as an important approach to identify chemical entities that have a high likelihood of binding to a target molecule to elicit desired bi... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566682 Wed, 01 Aug 2007 04:00:00 +0100 1566682 http://www.medworm.com/index.php?rid=1566681&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17696872%26dopt%3DAbstract Authors: Eriksson EM, Jackson DC The next generation of vaccines are being rationally designed according to rules that govern the way in which antigen is recognised by and stimulates the immune system. Amongst the first cells that encounter potentially dangerous agents such as viruses and bacteria are cells of the innate immune system, such as dendritic cells, that are widely distributed throughout the body including the skin. These cells patrol most tissues and have on their surface an array of receptors that have evolved to recognise many of the surface features of pathogens including the lipids and carbohydrates of structural lipoproteins, glycolipids and glycoproteins. Once encountered, recognised and engaged by a particular receptor on the dendritic cell, pathogenic material may t... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566681 Wed, 01 Aug 2007 04:00:00 +0100 1566681 http://www.medworm.com/index.php?rid=1566693&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17584118%26dopt%3DAbstract Authors: Carugo O Surprisingly, after at least two decades of researches focused on the analysis of the similarity between protein three-dimensional structures, several new comparison methods were proposed during the last few years. These are briefly summarized and commented below. Some of the newly developed techniques are fast and were designed to handle large amounts of data and vast structural databases. Other methods are much slower and were developed to gain biological information by comparing distantly related protein structures. Additional studies were devoted to the problem of the multiple structural alignments and to strategies of comparison between alternative structural alignments. PMID: 17584118 [PubMed - indexed for MEDLINE] (Source: Current Protein and Peptide Scienc... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566693 Fri, 01 Jun 2007 04:00:00 +0100 1566693 http://www.medworm.com/index.php?rid=1566692&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17584119%26dopt%3DAbstract Authors: Tsai CH, Chan CH, Chen BJ, Kao CY, Liu HL, Hsu JP Protein structure prediction with computational methods has gained much attention in the research fields of protein engineering and protein folding studies. Due to the vastness of conformational space, one of the major tasks is to restrain the flexibility of protein structure and reduce the search space. Many studies have revealed that, with the information of disulfide connectivity available, the search in conformational space can be dramatically reduced and lead to significant improvements in the prediction accuracy. As a result, predicting disulfide connectivity using bioinformatics approaches is of great interest nowadays. In this mini-review, the prediction of disulfide connectivity in proteins will be discussed in four as... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566692 Fri, 01 Jun 2007 04:00:00 +0100 1566692 http://www.medworm.com/index.php?rid=1566691&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17584120%26dopt%3DAbstract Authors: Naeem A, Saleemuddin M, Khan RH Glycoconjugates comprise a variety of structures, include glycoproteins and glycolipids and are found on the surfaces of animal and plant cells, as well as on the surface of microorganisms. Determination of the structure and the distribution of glycoconjugates on cell surfaces are important for the understanding their biological function. Lectins are useful to investigate protein-carbohydrate interactions, because they have specificity for defined carbohydrate structure. They have been implicated in cell-to-cell recognition and signaling, blood group typing, in immune recognition process, and various other biological processes, such as viral, bacterial, mycoplasmal and parasitic infections, fertilization, cancer metastasis, growth and differenti... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566691 Fri, 01 Jun 2007 04:00:00 +0100 1566691 http://www.medworm.com/index.php?rid=1566690&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17584121%26dopt%3DAbstract Authors: Nagradova N In live cells, protein folding often cannot occur spontaneously, but requires the participation of helper proteins - molecular chaperones and foldases. The mechanisms employed by chaperones markedly increase the effectiveness of protein folding, but have no bearing on the rate of this process, whereas foldases actually accelerate protein folding by exerting a direct influence on the rate-limiting steps of the overall reaction. Two types of foldases are known, using different principles of action. Peptidyl-prolyl cis/trans isomerase and protein-disulfide isomerase catalyze the folding of every protein that needs isomerization of prolyl peptide bonds or formation and isomerization of disulfide bonds for proper folding. By contrast, some foldases operating in the peri... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566690 Fri, 01 Jun 2007 04:00:00 +0100 1566690 http://www.medworm.com/index.php?rid=1566689&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17584122%26dopt%3DAbstract Authors: Sami AJ Somatotropin, commonly known as growth hormone (GH) is a polypeptide chain containing about 190 amino acid residues, produced by the pituitary gland in mammals and is responsible for a number of anabolic processes. It has two disulphide bridges, with 4 alpha helices arranged in anti-parallel distinctive manner. GH molecule binds with two receptor molecules to exhibit its full biological activity. In this review, the information regarding characterization, structure and function is updated. A number of human growth hormone variants (naturally occurring and produced by recombinant DNA- technology) are visualised, and structure related functions are revealed. 1) The di-sulphide bridges are not essential for the biological activity of the molecule. The two chain variants o... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566689 Fri, 01 Jun 2007 04:00:00 +0100 1566689 http://www.medworm.com/index.php?rid=1566688&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17584123%26dopt%3DAbstract Authors: Stehlik C The Death Domain Fold superfamily of evolutionarily conserved protein-protein interaction domains consists of 4 subfamilies: the death domain, the death effector domain, the caspase recruitment domain, and the PYRIN domain. Interaction of Death Domain Fold containing proteins modulates the activity of several downstream effectors, such as caspases and transcription factors. Recent studies provide evidence for not only homotypic-, but also heterotypic interactions among different sub-families, and even unconventional non-death domain fold interactions. As the number of potential protein associations among Death Domain Fold containing proteins expands and their influence on cellular responses increases, a challenging field for new investigations opens up. This review w... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566688 Fri, 01 Jun 2007 04:00:00 +0100 1566688 http://www.medworm.com/index.php?rid=1566702&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17430194%26dopt%3DAbstract Authors: Smialowski P, Martin-Galiano AJ, Cox J, Frishman D Efficient target selection methods are an important prerequisite for increasing the success rate and reducing the cost of high-throughput structural genomics efforts. There is a high demand for sequence-based methods capable of predicting experimentally tractable proteins and filtering out potentially difficult targets at different stages of the structural genomic pipeline. Simple empirical rules based on anecdotal evidence are being increasingly superseded by rigorous machine-learning algorithms. Although the simplicity of less advanced methods makes them more human understandable, more sophisticated formalized algorithms possess superior classification power. The quickly growing corpus of experimental success and failure dat... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566702 Sun, 01 Apr 2007 04:00:00 +0100 1566702 http://www.medworm.com/index.php?rid=1566701&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17430195%26dopt%3DAbstract Authors: Bourhis JM, Canard B, Longhi S In the last years there has been an increasing amount of experimental evidence pointing out that a large number of proteins are either fully or partially disordered (unstructured). Intrinsically disordered proteins are ubiquitary proteins that fulfil essential biological functions while lacking highly populated and uniform secondary and tertiary structure under physiological conditions. Despite the large abundance of disorder, disordered regions are still poorly detected. Recognition of disordered regions in a protein is instrumental for reducing spurious sequence similarity between disordered regions and ordered ones, and for delineating boundaries of protein domains amenable to crystallization. As presently none of the available automated metho... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566701 Sun, 01 Apr 2007 04:00:00 +0100 1566701 http://www.medworm.com/index.php?rid=1566700&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17430196%26dopt%3DAbstract Authors: Quevillon-Cheruel S, Leulliot N, Gentils L, van Tilbeurgh H, Poupon A The failure to produce and/or crystallize proteins is often due to their modular structure. There exists therefore considerable interest to develop strategies for tailoring proteins into crystallizable domains. In the framework of a Structural Genomics Project on soluble yeast proteins, we have tested the expression of numerous genetic constructs of our targets in order to produce and crystallize proteins and protein domains and solve their three-dimensional structure. In some cases, the choice of the domain boundaries was guided by prediction from sequence using various software packages, including Prelink, a home-made prediction method for detecting unfolded regions. In other cases, large numbers of constr... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566700 Sun, 01 Apr 2007 04:00:00 +0100 1566700 http://www.medworm.com/index.php?rid=1566699&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17430197%26dopt%3DAbstract Authors: Dosztányi Z, Sándor M, Tompa P, Simon I Intrinsically disordered/unstructured proteins exist in a highly flexible conformational state largely devoid of secondary structural elements and tertiary contacts. Despite their lack of a well defined structure, these proteins often fulfill essential regulatory functions. The intrinsic lack of structure confers functional advantages on these proteins, allowing them to adopt multiple conformations and to bind to different binding partners. The structural flexibility of disordered regions hampers efforts solving structures at high resolution by X-ray crystallography and/or NMR. Removing such proteins/regions from high-throughput structural genomics pipelines would be of significant benefit in terms of cost and success rate. In ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566699 Sun, 01 Apr 2007 04:00:00 +0100 1566699 http://www.medworm.com/index.php?rid=1566698&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17430198%26dopt%3DAbstract Authors: Csizmók V, Dosztányi Z, Simon I, Tompa P Intrinsically unstructured/disordered proteins (IUPs) and protein domains lack a well-defined three-dimensional structure under physiological conditions. Structural disorder imparts advantages in many non-conventional functions, which poses a significant challenge to our understanding of the structure-function relationship of proteins. The general appreciation of this fact, however, is hampered by the large gap in our knowledge on IUPs, as we have biophysical data on less than 500 of them, whereas bioinformatic predictions suggest at least several thousand such proteins in the human proteome alone. Thus, proteomic-scale identification and characterization of IUPs will need to be implemented to fill this gap and advance our kno... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566698 Sun, 01 Apr 2007 04:00:00 +0100 1566698 http://www.medworm.com/index.php?rid=1566697&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17430199%26dopt%3DAbstract Authors: Bryson K, Cozzetto D, Jones DT Domain prediction from sequence is a particularly challenging task, and currently, a large variety of different methodologies are employed to tackle the task. Here we try to classify these diverse approaches into a number of broad categories. Completely automatic domain prediction from sequence alone is currently fraught with problems, but this should not be so surprising since human experts currently have significant disagreement on domain assignment even when given the structures. It can be argued that we should only test the domain prediction methods on benchmark data that human experts agree upon and this is the approach we take in this paper. Even for the data sets on which human experts agree, automatic structure-based domain assignment sti... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566697 Sun, 01 Apr 2007 04:00:00 +0100 1566697 http://www.medworm.com/index.php?rid=1566696&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17430200%26dopt%3DAbstract Authors: Dovidchenko NV, Lobanov MY, Galzitskaya OV Prediction of protein domain boundaries is an important step for the prediction of three-dimensional structure. The simple method PDP has been elaborated for prediction of the number and position of domain boundaries in multi-domain proteins by use of amino acid sequence alone. The method uses an optimized scale based on the statistics of appearance of amino acid residues at domain boundaries. Our method demonstrates promising results in comparison to other methods that do not use homologous sequences. From the database of proteins that are targets from CASP6 (Critical Assessment of Techniques for Protein Structure Prediction) our program correctly assigned the number of domains for approximately 80% of one domain proteins and approxi... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566696 Sun, 01 Apr 2007 04:00:00 +0100 1566696 http://www.medworm.com/index.php?rid=1566695&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17430201%26dopt%3DAbstract Authors: Eisenhaber B, Eisenhaber F Given the huge number of sequences of otherwise uncharacterized protein sequences, computer-aided prediction of posttranslational modifications (PTMs) and translocation signals from amino acid sequence becomes a necessity. We have contributed to this multi-faceted, worldwide effort with the development of predictors for GPI lipid anchor sites, for N-terminal N-myristoylation sites, for farnesyl and geranylgeranyl anchor attachment as well as for the PTS1 peroxisomal signal. Although the substrate protein sequence signals for various PTMs or translocation systems vary dramatically, we found that their principal architecture is similar for all the cases studied. Typically, a small stretch of the amino acid residues is buried in the catalytic cleft of t... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566695 Sun, 01 Apr 2007 04:00:00 +0100 1566695 http://www.medworm.com/index.php?rid=1566694&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17430202%26dopt%3DAbstract Authors: Kambach C With recent advances in the technology and software underlying crystallographic structure solution, demands on both output and functional significance of X-ray structures are soaring. To achieve the required speed and quality also with ever larger and more difficult targets, combining HTP screening methods (robotics based or not) adopted from structural genomics initiatives with thorough expertise and dedicated characterization effort for each individual target is almost a must. I present concepts, practical considerations, and experiences on implementing an HTP technology platform for structural and functional studies on complexes, membrane proteins and other challenging targets. Emphasis lies on the environment of small academic groups engaged exclusively in hypoth... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566694 Sun, 01 Apr 2007 04:00:00 +0100 1566694 http://www.medworm.com/index.php?rid=1566711&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17305556%26dopt%3DAbstract Authors: Razeghifard R, Wallace BB, Pace RJ, Wydrzynski T Much is now known about how protein folding occurs, through the sequence analysis of proteins of known folding geometry and the sequence/structural analysis of proteins and their mutants. This has allowed not only the modification of natural proteins but also the construction of de novo polypeptides with predictable folding patterns. Structure/function analysis of natural proteins is used to construct derived versions that retain a degree of biological activity. The constructed versions made of either natural or artificial sequences contain critical residues for activity such as receptor binding. In some cases, the functionality is introduced by incorporating binding sites for other elements, such as organic cofactors or transit... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566711 Thu, 01 Feb 2007 05:00:00 +0100 1566711 http://www.medworm.com/index.php?rid=1566710&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17305557%26dopt%3DAbstract Authors: Wanga QM, Chen SH As the major cause of the common cold in children and adults, human rhinoviruses (HRVs) are a group of small single-stranded positive-sense RNA viruses. HRVs translate their genetic information into a polyprotein precursor that is mainly processed by a virally encoded 3C protease (3Cpro) to generate functional viral proteins and enzymes. It has been shown that the enzymatic activity of HRV 3Cpro is essential to viral replication. The 3Cpro is distinguished from most other proteases by the fact that it has a cysteine nucleophile but with a chymotrypsin-like serine protease folding. This unique protein structure together with its essential role in viral replication made the 3Cpro an excellent target for antiviral intervention. In recent years, considerable effo... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566710 Thu, 01 Feb 2007 05:00:00 +0100 1566710 http://www.medworm.com/index.php?rid=1566709&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17305558%26dopt%3DAbstract Authors: Fadiel A, Eichenbaum KD, Hamza A, Tan O, Lee HH, Naftolin F Electrostatic and electrochemical properties of bio-molecules, such as proteins, are governed by energy parameters that are, in part dependent on its folding. Disruption of this process can lead to the development of complex, multisystem diseases whose presentation may be organ-dependent. Examples include cystic fibrosis, alpha-1 antitrypsin deficiency, and Alzheimer disease. In addition to explaining exotic pathologic syndromes, an understanding of protein folding mechanisms may facilitate the understanding of less complex diseases and allow the development of novel therapeutic approaches. PMID: 17305558 [PubMed - indexed for MEDLINE] (Source: Current Protein and Peptide Science) Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566709 Thu, 01 Feb 2007 05:00:00 +0100 1566709 http://www.medworm.com/index.php?rid=1566708&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17305559%26dopt%3DAbstract Authors: Guilherme L, Faé KC, Oshiro SE, Tanaka AC, Pomerantzeff PM, Kalil J Molecular mimicry between streptococcal and human proteins has been proposed as the triggering factor leading to autoimmunity in rheumatic fever (RF) and rheumatic heart disease (RHD). In this review we focus on the studies on genetic susceptibility markers involved in the development of RF/RHD and molecular mimicry mediated by T cell responses of RHD patients against streptococcal antigens and human tissue proteins. We identified several M protein epitopes recognized by peripheral T cells of RF/RHD patients and by heart tissue infiltrating T cell clones of severe RHD patients. The regions of the M protein preferentially recognized by human T cells were also recognized by murine T cells. By analyzing the ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566708 Thu, 01 Feb 2007 05:00:00 +0100 1566708 http://www.medworm.com/index.php?rid=1566707&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17305560%26dopt%3DAbstract Authors: Schneider D, Finger C, Prodöhl A, Volkmer T Despite a wide variety of biological functions, alpha-helical membrane proteins display a rather simple transmembrane architecture. Although not many high resolution structures of transmembrane proteins are available today, our understanding of membrane protein folding has emerged in the recent years. Now we begin to develop a basic understanding of the forces that guide folding and interaction of alpha-helical membrane proteins. Some structural requirements for transmembrane helix interactions are defined, and common motifs have been discovered in the recent years which can drive helix-helix interactions. Nevertheless, many open questions remain to be addressed in future studies. One general problem with investigating transmemb... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566707 Thu, 01 Feb 2007 05:00:00 +0100 1566707 http://www.medworm.com/index.php?rid=1566706&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17305561%26dopt%3DAbstract Authors: Galdiero S, Galdiero M, Pedone C Membrane proteins, although constituting about one-third of all proteins encoded by the genomes of living organisms, are still strongly underrepresented in the database of 3D protein structures, which reflects the big challenge presented by this class of proteins. Structural biologists, by employing electron and x-ray approaches, are continuously revealing new and fundamental insights into the structure, function, assembly and interaction with lipids of membrane proteins. To date, two structural motifs, alpha-helices and beta-sheets, have been found in membrane proteins and interestingly these two structural motives correlate with the location: while alpha-helical bundles are most often found in the receptors and ion channels of plasma and endo... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566706 Thu, 01 Feb 2007 05:00:00 +0100 1566706 http://www.medworm.com/index.php?rid=1566705&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17305562%26dopt%3DAbstract Authors: Ronga L, Palladino P, Costantini S, Facchiano A, Ruvo M, Benedetti E, Ragone R, Rossi F The physiological form of the prion protein is normally expressed in mammalian cell and is highly conserved among species, although its role in cellular function remains elusive. Available evidence suggests that this protein is essential for neuronal integrity in the brain, possibly with a role in copper metabolism and cellular response to oxidative stress. In prion diseases, the benign cellular form of the protein is converted into an insoluble, protease-resistant abnormal scrapie form. This conversion parallels a conformational change of the polypeptide from a predominantly alpha-helical to a highly beta-sheet secondary structure. The scrapie form accumulates in the central nervous system... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566705 Thu, 01 Feb 2007 05:00:00 +0100 1566705 http://www.medworm.com/index.php?rid=1566704&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17305563%26dopt%3DAbstract Authors: Ceciliani F, Pocacqua V Glycosylation is one of the most important post-translational modifications of proteins, and has been widely acknowledged as one of the most important ways to modulate both protein function and lifespan. The acute phase proteins are a major group of serum proteins whose concentration is altered during various pathophysiological conditions. The aim of this paper is to review the structure and functions of the alpha1-acid glycoprotein (AGP). AGP belongs to the subfamily of immunocalins, a group of binding proteins that also have immunomodulatory functions. One of the most interesting features of AGP is that its glycosylation microheterogeneity can be modified during diseases. This aspect is particularly remarkable, since both the immunomodulatory and the ... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566704 Thu, 01 Feb 2007 05:00:00 +0100 1566704 http://www.medworm.com/index.php?rid=1566703&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17305564%26dopt%3DAbstract Authors: Tanabe S Allergic diseases affect atopic individuals, who synthesize specific Immunoglobulins E (IgE) to environmental allergens, usually proteins or glycoproteins. These allergens include grass and tree pollens, indoor allergens such as house dust mites and animal dander, and various foods. Because allergen-specific IgE antibodies are the main effector molecules in the immune response to allergens, many studies have focused on the identification of IgE-binding epitopes (called B cell epitopes), specific and minimum regions of allergen molecules that binds to IgE. Our initial studies have provided evidence that only four to five amino acid residues are enough to comprise an epitope, since pentapeptide QQQPP in wheat glutenin is minimally required for IgE binding. Afterwards, v... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566703 Thu, 01 Feb 2007 05:00:00 +0100 1566703 http://www.medworm.com/index.php?rid=1566722&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17168779%26dopt%3DAbstract Authors: Phoenix D, Harris F PMID: 17168779 [PubMed - indexed for MEDLINE] (Source: Current Protein and Peptide Science) Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566722 Fri, 01 Dec 2006 05:00:00 +0100 1566722 http://www.medworm.com/index.php?rid=1566721&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17168780%26dopt%3DAbstract Authors: Castro MS, Cilli EM, Fontes W Antimicrobial peptides (AMPs) are effector molecules of innate immune systems found in different groups of organisms, including microorganisms, plants, insects, amphibians and humans. These peptides exhibit several structural motifs but the most abundant AMPs assume an amphipathic alpha-helical structure. The alpha-helix forming antimicrobial peptides are excellent candidates for protein engineering leading to an optimization of their biological activity and target specificity. Nowadays several approaches are available and this review deals with the use of combinatorial synthesis and directed evolution in order to provide a high-throughput source of antimicrobial peptides analogues with enhanced lytic activity and specificity. PMID: 17168780 [... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566721 Fri, 01 Dec 2006 05:00:00 +0100 1566721 http://www.medworm.com/index.php?rid=1566720&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17168781%26dopt%3DAbstract Authors: Shai Y, Makovitzky A, Avrahami D Endogenous peptide antibiotics (termed also host-defense or antimicrobial peptides) are known as evolutionarily old components of innate immunity. They were found initially in invertebrates, but later on also in vertebrates, including humans. This secondary, chemical immune system provides organisms with a repertoire of small peptides that act against invasion (for both offensive and defensive purposes) by occasional and obligate pathogens. Each antimicrobial peptide has a broad but not identical spectrum of antimicrobial activity, predominantly against bacteria, providing the host maximum coverage against a rather broad spectrum of microbial organisms. Many of these peptides interact with the target cell membranes and increase their permeabili... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566720 Fri, 01 Dec 2006 05:00:00 +0100 1566720 http://www.medworm.com/index.php?rid=1566719&cid=s_37257_60_f&fid=37257&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17168782%26dopt%3DAbstract Authors: Dennison SR, Whittaker M, Harris F, Phoenix DA Cancer is a major cause of premature death and there is an urgent need for new anticancer agents with novel mechanisms of action. Here we review recent studies on a group of peptides that show much promise in this regard, exemplified by arthropod cecropins and amphibian magainins and aureins. These molecules are alpha-helical defence peptides, which show potent anticancer activity (alpha-ACPs) in addition to their established roles as antimicrobial factors and modulators of innate immune systems. Generally, alpha-ACPs exhibit selectivity for cancer and microbial cells primarily due to their elevated levels of negative membrane surface charge as compared to non-cancerous eukaryotic cells. The anticancer activity of alpha-ACPs norma... Current Protein and Peptide Science journals http://www.medworm.com/rss/comments.php?id=1566719 Fri, 01 Dec 2006 05:00:00 +0100 1566719