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Simplified Computational Methods for the Analysis of Protein Flexibility.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 revie...
Source: Current Protein and Peptide Science - June 28, 2009 Category: Biochemistry Authors: Kuznetsov IB Tags: Curr Protein Pept Sci Source Type: journals

The Role of Thiols and Disulfides on Protein Stability.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 sta...
Source: Current Protein and Peptide Science - June 28, 2009 Category: Biochemistry Authors: Trivedi MV, Laurence JS, Siahaan TJ Tags: Curr Protein Pept Sci Source Type: journals

Recent Progress in Research on Ribosome Inactivating Proteins.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Current Protein and Peptide Science - June 28, 2009 Category: Biochemistry Authors: Ng TB, Wong JH, Wang H Tags: Curr Protein Pept Sci Source Type: journals

Evolution of Mannose 6-Phosphate Receptors (MPR300 and 46): Lysosomal Enzyme Sorting Proteins.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Current Protein and Peptide Science - June 28, 2009 Category: Biochemistry Authors: Nadimpalli SK, Amancha PK Tags: Curr Protein Pept Sci Source Type: journals

Formation Mechanism of Insulin Fibrils and Structural Aspects of the Insulin Fibrillation Process.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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, descr...
Source: Current Protein and Peptide Science - June 28, 2009 Category: Biochemistry Authors: Groenning M, Frokjaer S, Vestergaard B Tags: Curr Protein Pept Sci Source Type: journals

Copper Binding Extrinsic to the Octarepeat Region in the Prion Protein.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Current Protein and Peptide Science - June 28, 2009 Category: Biochemistry Authors: Walter ED, Stevens DJ, Spevacek AR, Visconte MP, Dei Rossi A, Millhauser GL Tags: Curr Protein Pept Sci Source Type: journals

Light Chain Amyloidosis - Current Findings and Future Prospects.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Current Protein and Peptide Science - June 28, 2009 Category: Biochemistry Authors: Baden EM, Sikkink LA, Ramirez-Alvarado M Tags: Curr Protein Pept Sci Source Type: journals

Biophysics of Parkinson's Disease: Structure and Aggregation of alpha-Synuclein.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Current Protein and Peptide Science - June 28, 2009 Category: Biochemistry Authors: Uversky VN, Eliezer D Tags: Curr Protein Pept Sci Source Type: journals

Probing Early Events in Ferrous Cytochrome C Folding with Time-Resolved Natural and Magnetic Circular Dichroism Spectroscopies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Current Protein and Peptide Science - June 28, 2009 Category: Biochemistry Authors: Chen E, Goldbeck RA, Kliger DS Tags: Curr Protein Pept Sci Source Type: journals

Mechanisms and Consequences of Protein Aggregation: The Role of Folding Intermediates.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 de...
Source: Current Protein and Peptide Science - June 28, 2009 Category: Biochemistry Authors: Seshadri S, Oberg KA, Uversky VN Tags: Curr Protein Pept Sci Source Type: journals

beta-Lactamases-The Threat Renews.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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-lac...
Source: Current Protein and Peptide Science - June 28, 2009 Category: Biochemistry Authors: Livermore DM Tags: Curr Protein Pept Sci Source Type: journals

Cryoenzymology: Enzyme Action in Slow Motion.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Current Protein and Peptide Science - June 28, 2009 Category: Biochemistry Authors: Dunn BM, Uversky VN Tags: Curr Protein Pept Sci Source Type: journals

Acid Denaturation and Anion-Induced Folding of Globular Proteins: Multitude of Equilibium Partially Folded Intermediates.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Current Protein and Peptide Science - June 28, 2009 Category: Biochemistry Authors: Uversky VN, Goto Y Tags: Curr Protein Pept Sci Source Type: journals

The blueprint for Hsp70/Hsc70 molecular chaperones.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Current Protein and Peptide Science - June 28, 2009 Category: Biochemistry Authors: Witt SN Tags: Curr Protein Pept Sci Source Type: journals

Disaggregating Chaperones: An Unfolding Story.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Current Protein and Peptide Science - June 28, 2009 Category: Biochemistry Authors: Sharma SK, Christen P, Goloubinoff P Tags: Curr Protein Pept Sci Source Type: journals

Three Decades of the Class A beta-Lactamase Acyl-Enzyme.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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-lact...
Source: Current Protein and Peptide Science - June 28, 2009 Category: Biochemistry Authors: Fisher JF, Mobashery S Tags: Curr Protein Pept Sci Source Type: journals

Crystallographic Cryoenzymology and the Legacy of Tony Fink.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 qual...
Source: Current Protein and Peptide Science - June 28, 2009 Category: Biochemistry Authors: Petsko GA Tags: Curr Protein Pept Sci Source Type: journals

Enhanced alpha-Synuclein Expression in Human Eurodegenerative Diseases: Pathogenetic and Therapeutic Implications.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 pathogen...
Source: Current Protein and Peptide Science - June 28, 2009 Category: Biochemistry Authors: McCormack AL, Di Monte DA Tags: Curr Protein Pept Sci Source Type: journals

The classic basic protein of myelin - conserved structural motifs and the dynamic molecular barcode involved in membrane adhesion and protein-protein interactions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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-domai...
Source: Current Protein and Peptide Science - May 31, 2009 Category: Biochemistry Authors: Harauz G, Libich DS Tags: Curr Protein Pept Sci Source Type: journals

Quality assessment of protein structure models.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Current Protein and Peptide Science - May 31, 2009 Category: Biochemistry Authors: Kihara D, Chen H, Yang YD Tags: Curr Protein Pept Sci Source Type: journals

Methods for Calculating the Entropy and Free Energy and their Appli-cation to Problems Involving Protein Flexibility and Ligand Binding.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Current Protein and Peptide Science - May 31, 2009 Category: Biochemistry Authors: Meirovitch H, Cheluvaraja S, White RP Tags: Curr Protein Pept Sci Source Type: journals

The importance of being flexible: the case of basic region leucine zipper transcriptional regulators.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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. Transcriptio...
Source: Current Protein and Peptide Science - May 31, 2009 Category: Biochemistry Authors: Miller M Tags: Curr Protein Pept Sci Source Type: journals

A guide to template based structure prediction.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Current Protein and Peptide Science - May 31, 2009 Category: Biochemistry Authors: Qu X, Swanson R, Day R, Tsai J Tags: Curr Protein Pept Sci Source Type: journals

Predicting affinity and specificity of antigenic Peptide binding to major histocompatibility class I molecules.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 p...
Source: Current Protein and Peptide Science - May 31, 2009 Category: Biochemistry Authors: Sieker F, May A, Zacharias M Tags: Curr Protein Pept Sci Source Type: journals

Intra- and intermolecular communications in proteins.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19355977 [PubMed - in process] (Source: Current Protein and Peptide Science)
Source: Current Protein and Peptide Science - April 1, 2009 Category: Biochemistry Authors: De Benedetti PG Tags: Curr Protein Pept Sci Source Type: journals

Allosteric coupling and conformational fluctuations in proteins.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 repres...
Source: Current Protein and Peptide Science - April 1, 2009 Category: Biochemistry Authors: Onaran HO, Costa T Tags: Curr Protein Pept Sci Source Type: journals

Frameworks for understanding long-range intra-protein communication.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 b...
Source: Current Protein and Peptide Science - April 1, 2009 Category: Biochemistry Authors: Whitley MJ, Lee AL Tags: Curr Protein Pept Sci Source Type: journals

Allosteric Transitions in Biological Nanomachines are Described by Robust Normal Modes of Elastic Networks.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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: 1935...
Source: Current Protein and Peptide Science - April 1, 2009 Category: Biochemistry Authors: Zheng W, Brooks BR, Thirumalai D Tags: Curr Protein Pept Sci Source Type: journals

Protein domains as information processing units.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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. Fi...
Source: Current Protein and Peptide Science - April 1, 2009 Category: Biochemistry Authors: Lenaerts T, Schymkowitz J, Rousseau F Tags: Curr Protein Pept Sci Source Type: journals

Intra and inter-molecular communications through protein structure network.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 gl...
Source: Current Protein and Peptide Science - April 1, 2009 Category: Biochemistry Authors: Vishveshwara S, Ghosh A, Hansia P Tags: Curr Protein Pept Sci Source Type: journals

Perturbation waves in proteins and protein networks: applications of percolation and game theories in signaling and drug design.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 f...
Source: Current Protein and Peptide Science - April 1, 2009 Category: Biochemistry Authors: Antal MA, Böde C, Csermely P Tags: Curr Protein Pept Sci Source Type: journals

Computational Modeling of Intramolecular and Intermolecular Communication in GPCRs.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 communi...
Source: Current Protein and Peptide Science - April 1, 2009 Category: Biochemistry Authors: Fanelli F, De Benedetti PG, Raimondi F, Seeber M Tags: Curr Protein Pept Sci Source Type: journals

Ligand-receptor communication and drug design.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 a...
Source: Current Protein and Peptide Science - April 1, 2009 Category: Biochemistry Authors: De Benedetti PG, Fanelli F Tags: Curr Protein Pept Sci Source Type: journals

Improving our understanding of diabetes mellitus.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19275666 [PubMed - in process] (Source: Current Protein and Peptide Science)
Source: Current Protein and Peptide Science - February 1, 2009 Category: Biochemistry Authors: Leung PS, de Gasparo M Tags: Curr Protein Pept Sci Source Type: journals

Ghrelin and metabolic disorders.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 a...
Source: Current Protein and Peptide Science - February 1, 2009 Category: Biochemistry Authors: Ukkola O Tags: Curr Protein Pept Sci Source Type: journals

Aminoacid support in the prevention of diabetes and diabetic complications.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 pathway...
Source: Current Protein and Peptide Science - February 1, 2009 Category: Biochemistry Authors: Anuradha CV Tags: Curr Protein Pept Sci Source Type: journals

Connexins, diabetes and the metabolic syndrome.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 d...
Source: Current Protein and Peptide Science - February 1, 2009 Category: Biochemistry Authors: Hamelin R, Allagnat F, Haefliger JA, Meda P Tags: Curr Protein Pept Sci Source Type: journals

The roles of the PDZ-containing proteins bridge-1 and PDZD2 in the regulation of insulin production and pancreatic beta-cell mass.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 signal...
Source: Current Protein and Peptide Science - February 1, 2009 Category: Biochemistry Authors: Thomas MK, Tsang SW, Yeung ML, Leung PS, Yao KM Tags: Curr Protein Pept Sci Source Type: journals

The role of islet neogeneis-associated protein (INGAP) in pancreatic islet neogenesis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Current Protein and Peptide Science - February 1, 2009 Category: Biochemistry Authors: Pittenger GL, Taylor-Fishwick D, Vinik AI Tags: Curr Protein Pept Sci Source Type: journals

Incretin-based therapy of type 2 diabetes mellitus.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 th...
Source: Current Protein and Peptide Science - February 1, 2009 Category: Biochemistry Authors: Knop FK, Vilsbøll T, Holst JJ Tags: Curr Protein Pept Sci Source Type: journals

The endocannabinoid system: a promising target for the management of type 2 diabetes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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,...
Source: Current Protein and Peptide Science - February 1, 2009 Category: Biochemistry Authors: Scheen AJ Tags: Curr Protein Pept Sci Source Type: journals

Angiotensin II in type 2 diabetes mellitus.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 g...
Source: Current Protein and Peptide Science - February 1, 2009 Category: Biochemistry Authors: Chu KY, Leung PS Tags: Curr Protein Pept Sci Source Type: journals

Heat shock proteins in diabetes and wound healing.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 clea...
Source: Current Protein and Peptide Science - February 1, 2009 Category: Biochemistry Authors: Atalay M, Oksala N, Lappalainen J, Laaksonen DE, Sen CK, Roy S Tags: Curr Protein Pept Sci Source Type: journals

Role of resistin in insulin sensitivity in rodents and humans.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 hum...
Source: Current Protein and Peptide Science - February 1, 2009 Category: Biochemistry Authors: Barnes KM, Miner JL Tags: Curr Protein Pept Sci Source Type: journals

Plasma gelsolin: function, prognostic value, and potential therapeutic use.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 inf...
Source: Current Protein and Peptide Science - December 1, 2008 Category: Biochemistry Authors: Bucki R, Levental I, Kulakowska A, Janmey PA Tags: Curr Protein Pept Sci Source Type: journals

Thermal adaptation of heat shock proteins.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ch...
Source: Current Protein and Peptide Science - December 1, 2008 Category: Biochemistry Authors: Muga A, Moro F Tags: Curr Protein Pept Sci Source Type: journals

Advances and pitfalls in protein structure prediction.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Current Protein and Peptide Science - December 1, 2008 Category: Biochemistry Authors: Cozzetto D, Tramontano A Tags: Curr Protein Pept Sci Source Type: journals

The hemoglobins of fishes living at polar latitudes - current knowledge on structural adaptations in a changing environment.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 en...
Source: Current Protein and Peptide Science - December 1, 2008 Category: Biochemistry Authors: Verde C, Vergara A, Mazzarella L, di Prisco G Tags: Curr Protein Pept Sci Source Type: journals

Flexible Structures and Ligand Interactions of Tandem Repeats Consisting of Proline, Glycine, Asparagine, Serine, and/or Threonine Rich Oligopeptides in Proteins.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Current Protein and Peptide Science - December 1, 2008 Category: Biochemistry Authors: Matsushima N, Yoshida H, Kumaki Y, Kamiya M, Tanaka T, Izumi Y, Kretsinger RH Tags: Curr Protein Pept Sci Source Type: journals

The Retinal cGMP Phosphodiesterase gamma-Subunit - A Chameleon.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 inte...
Source: Current Protein and Peptide Science - December 1, 2008 Category: Biochemistry Authors: Guo LW, Ruoho AE Tags: Curr Protein Pept Sci Source Type: journals