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 Opinion in Chemical Biology' source. Thu, 09 Feb 2012 13:38:34 +0100 http://www.medworm.com/index.php?rid=5620627&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22260931%26dopt%3DAbstract Authors: Kim HJ, Ruszczycky MW, Liu HW Abstract Only a very few examples of enzymes known to catalyze pericyclic reactions have been reported, and presently no enzyme has been demonstrated unequivocally to catalyze a Diels-Alder reaction. Nevertheless, research into secondary metabolism has led to the discovery of numerous natural products exhibiting the structural hallmarks of [4+2] cycloadditions, prompting efforts to characterize the responsible enzymatic processes. These efforts have resulted in a growing collection of enzymes believed to catalyze pericyclic [4+2] cycloaddition reactions; however, in each case the complexity of the substrates and catalytic properties of these enzymes poses significant challenges in substantiating these hypotheses. Herein we consider the princip... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5620627 Tue, 17 Jan 2012 05:00:00 +0100 5620627 http://www.medworm.com/index.php?rid=5598650&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245533%26dopt%3DAbstract Authors: Abe I Abstract The structurally and mechanistically simple type III polyketide synthases (PKSs) catalyze iterative condensations of CoA thioesters to produce a variety of polyketide scaffolds with remarkably diverse structures and biological activities. By exploiting the enzymes, we combined precursor-directed biosynthesis with nitrogen-containing substrates and structure-based enzyme engineering and generated unnatural, novel polyketide-alkaloid scaffolds with promising biological activities. The nucleophilic nitrogen atom and the engineered enzymes thus facilitated the formation of additional CC and CN bonds during the enzymatic transformations. The methodology will contribute to the further production of chemically and structurally divergent, unnatural natural products,... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5598650 Fri, 13 Jan 2012 05:00:00 +0100 5598650 http://www.medworm.com/index.php?rid=5577916&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22226769%26dopt%3DAbstract Authors: Altelaar AM, Heck AJ Abstract Here we review recent developments and trends in sample preparation, pre-fractionation, chromatography and mass spectrometry contributing towards the ultra-sensitive global analysis of proteins. Highly sensitive MS-based proteomics is not only beneficiary for the proteome analysis of single cells, an aim which is getting into reach, but also clearly relevant for the analysis of (a) subcellular organelles, (b) specific low-abundant cell-types such as adult stem cells, and (c) smaller but more homogeneous cell populations sorted or dissected from (diseased) tissue. PMID: 22226769 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5577916 Fri, 06 Jan 2012 05:00:00 +0100 5577916 http://www.medworm.com/index.php?rid=5577918&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22221852%26dopt%3DAbstract Authors: Kolarich D, Lepenies B, Seeberger PH Abstract Glycomics and glycoproteomics have become indispensible tools in the study of glycoconjugates. Mass spectrometry based methods are standardly used to study the proteome and/or glycome and these approaches are capable of providing both, qualitative and quantitative information using top down techniques. The human immune system marks a particular area of interest for glycomics and glycoproteomics research since a large number of key proteins in innate and adaptive immunity are glycoproteins. In numerous examples, the crucial influence of glycosylation on critical steps such as receptor interaction and binding has been demonstrated. In this review, we focus on different glycomics and glycoproteomics approaches and their applicatio... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5577918 Tue, 03 Jan 2012 05:00:00 +0100 5577918 http://www.medworm.com/index.php?rid=5577917&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22221853%26dopt%3DAbstract Authors: Foong YM, Fu J, Yao SQ, Uttamchandani M Abstract Microarrays offer a compact solution for massively parallel screening. In recent years, microarrays have branched away from the exclusive pursuit of small molecule 'hits' in target centric screens, towards the sophisticated dissection of disease biology and comparative profiling of cellular states. This has led to innovative and instructive ways in which the platform may be deployed, providing new-found methods with which to harness the throughput achievable. Library design and diversity continues to drive success with peptide and small molecule microarrays. Newer synthesis and immobilization strategies extend the already wide repertoire of fabrication methods available. Herein we describe the latest advances in the small mo... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5577917 Tue, 03 Jan 2012 05:00:00 +0100 5577917 http://www.medworm.com/index.php?rid=5512451&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22119536%26dopt%3DAbstract Authors: Manley S, Gunzenhäuser J, Olivier N Abstract Super-resolution fluorescence imaging can be achieved through the localization of single molecules. By using suitable dyes, optical configurations, and software, it is possible to study a wide variety of biological systems. Here, we summarize the different approaches to labeling proteins. We review proven imaging modalities, and the features of freely available software. Finally, we give an overview of some biological applications. We conclude by synthesizing these different technical aspects into recommendations for standards that the field might apply to ensure quality of images and comparability of algorithms and dyes. PMID: 22119536 [PubMed - in process] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5512451 Thu, 01 Dec 2011 05:00:00 +0100 5512451 http://www.medworm.com/index.php?rid=5439144&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22104179%26dopt%3DAbstract Authors: Lowder MA, Appelbaum JS, Hobert EM, Schepartz A Abstract In recent years, scientists have expanded their focus from cataloging genes to characterizing the multiple states of their translated products. One anticipated result is a dynamic map of the protein association networks and activities that occur within the cellular environment. While in vitro-derived network maps can illustrate which of a multitude of possible protein-protein associations could exist, they supply a falsely static picture lacking the subtleties of subcellular location (where) or cellular state (when). Generating protein association network maps that are informed by both subcellular location and cell state requires novel approaches that accurately characterize the state of protein associations in livin... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5439144 Fri, 18 Nov 2011 05:00:00 +0100 5439144 http://www.medworm.com/index.php?rid=5439143&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22104180%26dopt%3DAbstract Authors: Schepartz A, Gonzalez RL PMID: 22104180 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5439143 Fri, 18 Nov 2011 05:00:00 +0100 5439143 http://www.medworm.com/index.php?rid=5439142&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22104181%26dopt%3DAbstract Authors: Perez CE, Gonzalez RL Abstract Combined with the availability of highly purified, fluorescently labeled in vitro translation systems, the advent of single-molecule fluorescence imaging has ushered in a new era in high-resolution mechanistic studies of ribosome-catalyzed protein synthesis, or translation. Together with ensemble biochemical investigations of translation and structural studies of functional ribosomal complexes, in vitro single-molecule fluorescence imaging of protein synthesis is providing unique mechanistic insight into this fundamental biological process. More recently, rapidly evolving breakthroughs in fluorescence-based molecular imaging in live cells with sub-diffraction-limit spatial resolution and ever-increasing temporal resolution provide great promi... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5439142 Fri, 18 Nov 2011 05:00:00 +0100 5439142 http://www.medworm.com/index.php?rid=5439146&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22098719%26dopt%3DAbstract Authors: Edgington LE, Verdoes M, Bogyo M Abstract Proteases are enzymes that cleave peptide bonds in protein substrates. This process can be important for regulated turnover of a target protein but it can also produce protein fragments that then perform other functions. Because the last few decades of protease research have confirmed that proteolysis is an essential regulatory process in both normal physiology and in multiple disease-associated conditions, there has been an increasing interest in developing methods to image protease activity. Proteases are also considered to be one of the few 'druggable' classes of proteins and therefore a large number of small molecule based inhibitors of proteases have been reported. These compounds serve as a starting point for the design of pr... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5439146 Wed, 16 Nov 2011 05:00:00 +0100 5439146 http://www.medworm.com/index.php?rid=5439145&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22098720%26dopt%3DAbstract Authors: Flors C, Earnshaw WC Abstract Chromatin organization spans a wide range of structural complexity. Substructures at the 10-200nm scale are poorly characterized, especially in living cells, due to the limitations of electron microscopy and standard optical microscopy. Recently developed super-resolution fluorescence microscopy methods represent an exciting opportunity to access those substructures, and recent progress with these techniques has yielded insights into chromatin organization at different condensation stages. Recent studies have focused on confronting the challenges that are specific to chromatin super-resolution imaging, such as the high packing density of mitotic chromosomes and difficulties in interpreting interphase chromatin images. Building on these first r... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5439145 Wed, 16 Nov 2011 05:00:00 +0100 5439145 http://www.medworm.com/index.php?rid=5418906&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22079663%26dopt%3DAbstract Authors: Lukinavičius G, Johnsson K Abstract Numerous synthetic fluorophores have been developed that can switch their spectroscopic properties upon interaction with other molecules or by irradiation with light. In recent years, protein-labeling techniques have been introduced that permit the specific attachment of such molecules to proteins of interest in living cells. We review here how the attachment of switchable fluorophores to selected proteins of interest via self-labeling protein tags enables new applications in different areas of biology and discuss how these molecules could be further improved. PMID: 22079663 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5418906 Fri, 11 Nov 2011 05:00:00 +0100 5418906 http://www.medworm.com/index.php?rid=5418907&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22079055%26dopt%3DAbstract Authors: Xu Y, Melia TJ, Toomre DK Abstract Cellular compartmentalization into discrete organelles is maintained by membrane trafficking including vesiculation and tubulation. Recent advances in superresolution imaging have begun to bring these small and dynamic events into focus. Most nanoscopes exploit, and are limited by, switching dyes ON and OFF. Using ground state depletion to switch dyes into long-lived dark states can exploit specific photophysical properties of dyes, such as redox potential or pK(a), and expand the repertoire of nanoscopy probes for multicolor imaging. Seeing is not enough, and new technologies based on homodimerization, heterodimerization and selective release can manipulate membrane trafficking in pulse-chase and light-controlled ways. Herein we highligh... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5418907 Thu, 10 Nov 2011 05:00:00 +0100 5418907 http://www.medworm.com/index.php?rid=5418908&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22078994%26dopt%3DAbstract Authors: Wysocki LM, Lavis LD Abstract Small molecule fluorophores are essential tools for chemical biology. A benefit of synthetic dyes is the ability to employ chemical approaches to control the properties and direct the position of the fluorophore. Applying modern synthetic organic chemistry strategies enables efficient tailoring of the chemical structure to obtain probes for specific biological experiments. Chemistry can also be used to activate fluorophores; new fluorogenic enzyme substrates and photoactivatable compounds with improved properties have been prepared that facilitate advanced imaging experiments with low background fluorescence. Finally, chemical reactions in live cells can be used to direct the spatial distribution of the fluorophore, allowing labeling of define... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5418908 Wed, 09 Nov 2011 05:00:00 +0100 5418908 http://www.medworm.com/index.php?rid=5418909&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22070901%26dopt%3DAbstract Authors: Shekhawat SS, Ghosh I Abstract It has been estimated that 650,000 protein-protein interactions exist in the human interactome (Stumpf et al., 2008 [1]), a subset of all possible macromolecular partnerships that dictate life. Thus there is a continued need for the development of sensitive and user-friendly methods for cataloguing biomacromolecules in complex environments and for detecting their interactions, modifications, and cellular location. Such methods also allow for establishing differences in the interactome between a normal and diseased cellular state and for quantifying the outcome of therapeutic intervention. A promising approach for deconvoluting the role of macromolecular partnerships is split-protein reassembly, also called protein fragment complementation. Th... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5418909 Mon, 07 Nov 2011 05:00:00 +0100 5418909 http://www.medworm.com/index.php?rid=5418911&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22057211%26dopt%3DAbstract Authors: Hoskins AA, Gelles J, Moore MJ Abstract Splicing is an essential eukaryotic process in which introns are excised from precursors to messenger RNAs and exons ligated together. This reaction is catalyzed by a multi-MegaDalton machine called the spliceosome, composed of 5 small nuclear RNAs (snRNAs) and a core set of ∼100 proteins minimally required for activity. Because of the spliceosome's size, its low abundance in cellular extracts, and its highly dynamic assembly pathway, analysis of the kinetics of splicing and the conformational rearrangements occurring during spliceosome assembly and disassembly has proven extraordinarily challenging. Here, we review recent progress in combining chemical biology methodologies with single molecule fluorescence techniques to provide a... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5418911 Fri, 04 Nov 2011 04:00:00 +0100 5418911 http://www.medworm.com/index.php?rid=5418910&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22057212%26dopt%3DAbstract Authors: Hengesbach M, Akiyama BM, Stone MD Abstract The telomerase ribonucleoprotein is a specialized reverse transcriptase required to maintain protective chromosome end-capping structures called telomeres. In most cells, telomerase is not active and the natural shortening of telomeres with each round of DNA replication ultimately triggers cell growth arrest. In contrast, the presence of telomerase confers a high level of renewal capacity upon rapidly dividing cells. Telomerase is aberrantly activated in 90% of human cancers and thus represents an important target for anticancer therapeutics. However, the naturally low abundance of telomerase has hampered efforts to obtain high-resolution models for telomerase structure and function. To circumvent these challenges, single-molecul... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5418910 Fri, 04 Nov 2011 04:00:00 +0100 5418910 http://www.medworm.com/index.php?rid=5418915&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22055494%26dopt%3DAbstract Authors: Bruchez MP Abstract Thirteen years after the demonstration of quantum dots as biological imaging agents, and nine years after the initial commercial introduction of bioconjugated quantum dots, the brightness and photostability of the quantum dots has enabled a range of investigations using single molecule tracking. These materials are being routinely utilized by a number of groups to track the dynamics of single molecules in reconstituted biophysical systems and on living cells, and are especially powerful for investigations of single molecules over long timescales with short exposure times and high pointing accuracy. New approaches are emerging where the quantum dots are used as 'hard-sphere' probes for intracellular compartments. Innovations in quantum dot surface modifi... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5418915 Thu, 03 Nov 2011 04:00:00 +0100 5418915 http://www.medworm.com/index.php?rid=5418914&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22055495%26dopt%3DAbstract Authors: Min W Abstract Imaging contrasts other than fluorescence are highly desirable for label-free detection and interrogation of nonfluorescent molecular species inside live cells, tissues, and organisms. The recently developed stimulated Raman scattering (SRS) and stimulated emission microscopy techniques provide sensitive and specific contrast mechanisms for nonfluorescent species, by employing the light amplification aspect of stimulated radiation. Compared to their spontaneous counterparts, stimulated radiation can enhance the imaging performance significantly, making the previously 'dark' molecules observable. Here we review and summarize the underlying principles of this emerging class of molecular imaging techniques. PMID: 22055495 [PubMed - as supplied by publisher]... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5418914 Thu, 03 Nov 2011 04:00:00 +0100 5418914 http://www.medworm.com/index.php?rid=5418913&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22055496%26dopt%3DAbstract Authors: Armitage BA Abstract Fluorescence microscopy and molecular tagging technologies have ushered in a new era in our understanding of protein localization and function in cells. This review summarizes recent efforts to extend some of these methods (and to create new ones) to imaging of RNA in live cells. Both fluorescent proteins and hybridization probes allow noncovalent labeling of specific RNA molecules with fluorescent dyes that allow detection and tracking in real time. PMID: 22055496 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5418913 Thu, 03 Nov 2011 04:00:00 +0100 5418913 http://www.medworm.com/index.php?rid=5418912&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22055497%26dopt%3DAbstract Authors: Lee JS, Vendrell M, Chang YT Abstract The development of optical probes is receiving considerable attention due to their rising adaptation in diagnostics and medical imaging. Diversity-oriented approaches make use of combinatorial chemistry and high-throughput screenings to enrich the spectral and structural variety of these probes and effectively identify those with specific properties (e.g. molecular affinity, cellular selectivity, high photostability, and sensitivity). Herein we review recent examples in which diversity-driven strategies have assisted the discovery of new molecular imaging probes. PMID: 22055497 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5418912 Thu, 03 Nov 2011 04:00:00 +0100 5418912 http://www.medworm.com/index.php?rid=5228631&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21920800%26dopt%3DAbstract Authors: Benkovic SJ, Raney KD PMID: 21920800 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5228631 Tue, 13 Sep 2011 04:00:00 +0100 5228631 http://www.medworm.com/index.php?rid=5218453&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907611%26dopt%3DAbstract Authors: Lee SJ, Richardson CC Abstract The replication system of phage T7 provides a model for DNA replication. Biochemical, structural, and single-molecule analyses together provide insight into replisome mechanics. A complex of polymerase, a processivity factor, and helicase mediates leading strand synthesis. Establishment of the complex requires an interaction of the C-terminal tail of the helicase with the polymerase. During synthesis the complex is stabilized by other interactions to provide for a processivity of 5 kilobase (kb). The C-terminal tail also interacts with a distinct region of the polymerase to captures dissociating polymerase to increase the processivity to >17kb. The lagging strand is synthesized discontinuously within a loop that forms and resolves during e... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5218453 Thu, 08 Sep 2011 04:00:00 +0100 5218453 http://www.medworm.com/index.php?rid=5218454&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21889903%26dopt%3DAbstract Authors: Hübscher U, Maga G Abstract Maintenance of genetic stability is of crucial importance for any form of life. Before cell division in each mammalian cell, the process of DNA replication must faithfully duplicate three billion bases with an absolute minimum of mistakes. This is complicated by the fact that DNA itself is highly reactive and is constantly attacked by endogenous and exogenous factors leading to 50,000-100,000 different damages in the DNA of human cells every day. In this mini-review we will focus on lesion bypass by DNA polymerase machines either in replication or repair, with particular focus on the repair of oxidative lesions. PMID: 21889903 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5218454 Thu, 01 Sep 2011 04:00:00 +0100 5218454 http://www.medworm.com/index.php?rid=5218455&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21880539%26dopt%3DAbstract Authors: Alexander MR, Gilmore IS PMID: 21880539 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5218455 Mon, 29 Aug 2011 04:00:00 +0100 5218455 http://www.medworm.com/index.php?rid=5175007&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21865075%26dopt%3DAbstract Authors: Patel SS, Pandey M, Nandakumar D Abstract Helicases are molecular motor proteins that couple NTP hydrolysis to directional movement along nucleic acids. A class of helicases characterized by their ring-shaped hexameric structures translocate processively and unidirectionally along single-stranded (ss) DNA to separate the strands of double-stranded (ds) DNA, aiding both in the initiation and fork progression during DNA replication. These replicative ring-shaped helicases are found from virus to human. We review recent biochemical and structural studies that have expanded our understanding on how hexameric helicases use the NTPase reaction to translocate on ssDNA, unwind dsDNA, and how their physical and functional interactions with the DNA polymerase and primase enzymes coo... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5175007 Sun, 21 Aug 2011 23:00:00 +0100 5175007 http://www.medworm.com/index.php?rid=5156896&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862382%26dopt%3DAbstract Authors: Ryan DP, Owen-Hughes T Abstract Chromatin facilitates the housing of eukaryotic DNA within the nucleus and restricts access to the underlying sequences. Thus, the regulation of chromatin structure provides an excellent platform for regulating processes that require information stored within genomic DNA. Snf2 proteins are a family of helicase-like proteins that direct energy derived from ATP hydrolysis into the mechanical remodelling of chromatin structure. Here, we highlight some of the recent discoveries regarding this family of proteins and show Snf2 proteins have roles in many aspects of genetic metabolism. Recent developments include new insights into the mechanism for nucleosome spacing and histone dimer exchange; together with growing evidence for the involvement of ... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5156896 Fri, 19 Aug 2011 23:00:00 +0100 5156896 http://www.medworm.com/index.php?rid=5156895&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862383%26dopt%3DAbstract Authors: Pyle AM Abstract It is becoming increasingly clear that RNA molecules play a major role in all aspects of metabolism. The conformational state and stability of RNA are controlled by RNA remodeling proteins, which are ubiquitous motor proteins in the cell. Here, we review advances in our understanding of the structure and function of three major structural families of RNA remodeling proteins, the hexameric ring proteins, the processive monomeric RNA translocase/helicases, and the functionally diverse DEAD-box remodeling proteins. New studies have revealed molecular mechanisms for coupling between ATP hydrolysis and unwinding, the physical basis for regulatory control by cofactors, and novel functions for RNA remodeling proteins. PMID: 21862383 [PubMed - as supplied by p... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5156895 Fri, 19 Aug 2011 23:00:00 +0100 5156895 http://www.medworm.com/index.php?rid=5156893&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862385%26dopt%3DAbstract Authors: Karbstein K Abstract Ribosome assembly involves rRNA transcription, modification, folding and cleavage from precursor transcripts, and association of ribosomal proteins (Rps). In bacteria, this complex process requires only a handful of proteins in addition to those needed for rRNA transcription, modification and cleavage, while in eukaryotes a large machinery comprising ∼200 proteins in the yeast S. cerevisiae has been identified. Furthermore, while the bacterial assembly factors generally produce only cold-sensitive phenotypes upon deletion, most of the eukaryotic assembly factors are essential, comprising ∼20% of essential yeast proteins. This review explores recent rapid progress in the structural and functional dissection of the 40S assembly machinery. PMID: 2... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5156893 Fri, 19 Aug 2011 23:00:00 +0100 5156893 http://www.medworm.com/index.php?rid=5156894&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862384%26dopt%3DAbstract Authors: Judge PJ, Watts A Abstract The plasma membrane functions as a semi-permeable barrier, defining the interior (or cytoplasm) of an individual cell. This highly dynamic and complex macromolecular assembly comprises predominantly lipids and proteins held together by entropic forces and provide the interface through which a cell interacts with its immediate environment. The extended sheet-like bilayer structure formed by the phospholipids is a highly adaptable platform whose structure and composition may be tuned to provide specialised functionality. Although a number of biophysical techniques including X-ray crystallography have been used to determine membrane protein structures, these methods are unable to replicate and accommodate the complexity and diversity of natural memb... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5156894 Thu, 18 Aug 2011 23:00:00 +0100 5156894 http://www.medworm.com/index.php?rid=5156891&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862386%26dopt%3DAbstract This article aims to explore basic physical concepts behind these experiments from a strictly practical point of using these data to extract meaningful information about the interactions. It also focuses on different loading regimes in these experiments, different kinetics that they cause, and different data interpretation that is required for measurements in those regimes. PMID: 21862386 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5156891 Thu, 18 Aug 2011 23:00:00 +0100 5156891 http://www.medworm.com/index.php?rid=5156869&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862387%26dopt%3DAbstract Authors: Kunkel TA Abstract Coordinated replication of eukaryotic nuclear genomes is asymmetric, with copying of a leading strand template preceding discontinuous copying of the lagging strand template. Replication is catalyzed by DNA polymerases α, δ and ɛ, enzymes that are related yet differ in physical and biochemical properties, including fidelity. Recent studies suggest that Pol ɛ is normally the primary leading strand replicase, whereas most synthesis by Pol δ occurs during lagging strand replication. New studies show that replication asymmetry can generate strand-specific genome instability resulting from biased deoxynucleotide pools and unrepaired ribonucleotides incorporated into DNA during replication, and that the eukaryotic replication machinery has evolved to most... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5156869 Thu, 18 Aug 2011 23:00:00 +0100 5156869 http://www.medworm.com/index.php?rid=5156898&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21855395%26dopt%3DAbstract Authors: McHenry CS Abstract Bacterial replicases are complex, tripartite replicative machines. They contain a polymerase, Pol III, a β(2) processivity factor and a DnaX complex ATPase that loads β(2) onto DNA and chaperones Pol III onto the newly loaded β(2). Many bacteria encode both a full length τ and a shorter γ form of DnaX by a variety of mechanisms. The polymerase catalytic subunit of Pol III, α, contains a PHP domain that not only binds to prototypical ɛ Mg(2+)-dependent exonuclease, but also contains a second Zn(2+)-dependent proofreading exonuclease, at least in some bacteria. Replication of the chromosomes of low GC Gram-positive bacteria require two Pol IIIs, one of which, DnaE, appears to extend RNA primers a only short distance before handing the product off t... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5156898 Wed, 17 Aug 2011 23:00:00 +0100 5156898 http://www.medworm.com/index.php?rid=5156897&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21856207%26dopt%3DAbstract Authors: Kaguni JM Abstract To initiate DNA replication, DnaA recognizes and binds to specific sequences within the Escherichia coli chromosomal origin (oriC), and then unwinds a region within oriC. Next, DnaA interacts with DnaB helicase in loading the DnaB-DnaC complex on each separated strand. Primer formation by primase (DnaG) induces the dissociation of DnaC from DnaB, which involves the hydrolysis of ATP bound to DnaC. Recent evidence indicates that DnaC acts as a checkpoint in the transition from initiation to the elongation stage of DNA replication. Freed from DnaC, DnaB helicase unwinds the parental duplex DNA while interacting the cellular replicase, DNA polymerase III holoenzyme, and primase as it intermittently forms primers that are extended by the replicase in duplica... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5156897 Tue, 16 Aug 2011 23:00:00 +0100 5156897 http://www.medworm.com/index.php?rid=5156899&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21852183%26dopt%3DAbstract Authors: Beattie TR, Bell SD Abstract The archaeal DNA replication apparatus is a simplified version of that of eukaryotes and has attracted attention as a tractable model system for the orthologous, but significantly more complex eukaryal machinery. A variety of archaeal model organisms have been investigated with strong emphasis on structural and biochemical analyses of replication-associated proteins. In this review we will describe recent advances in understanding the properties of the replicative helicase, the MCM complex, and the role of the sliding clamp, PCNA, in mediating a range of protein-DNA transactions. Although both complexes form ring shaped assemblies, they play very distinct roles at the leading and trailing edges of the replication fork machinery respectively. ... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5156899 Mon, 15 Aug 2011 23:00:00 +0100 5156899 http://www.medworm.com/index.php?rid=5141199&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21831695%26dopt%3DAbstract Authors: Kingshott P, Andersson G, McArthur SL, Griesser HJ Abstract The chemical composition of the surface layers of synthetic biomaterials used for human medical devices and in biotechnology plays a key role in determining interfacial interactions between biological media (such as protein solutions, cells, tissue) and the synthetic material. Accordingly, considerable research efforts focus on improving the 'biocompatibility' of biomaterials by applying various surface modification and thin film coating approaches. Here we focus on the patterning of surface chemistries, often designed to exercise spatial control over events such as cell attachment and spreading. Secondly, we review recent developments in chemical characterisation of biomaterials surfaces, which is essential both ... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5141199 Sun, 07 Aug 2011 23:00:00 +0100 5141199 http://www.medworm.com/index.php?rid=5141200&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21816660%26dopt%3DAbstract Authors: Collins K Abstract The eukaryotic ribonucleoprotein reverse transcriptase (RT) telomerase uses a template within its integral RNA subunit to extend chromosome ends by synthesis of single-stranded telomeric repeats. Telomerase is adapted to its unique cellular role by an ability to release product DNA in single-stranded form, regenerating free template from the product-template hybrid. Furthermore, by retaining a template-independent grip on the single-stranded product, telomerase can catalyze processive repeat synthesis. These specialized nucleic acid handling properties are dependent on the protein and RNA domain network within an active RNP. RNP domain architecture and mechanisms for single-stranded DNA handling have been a focus of recent studies highlighted here. P... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5141200 Mon, 01 Aug 2011 23:00:00 +0100 5141200 http://www.medworm.com/index.php?rid=5097617&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21783401%26dopt%3DAbstract Authors: Matter A, Keller TH PMID: 21783401 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5097617 Wed, 20 Jul 2011 23:00:00 +0100 5097617 http://www.medworm.com/index.php?rid=5051554&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21775192%26dopt%3DAbstract Authors: Deckert-Gaudig T, Deckert V Tip-enhanced Raman scattering (TERS) enables the label-free investigation of biochemical interfaces with nanometer lateral resolution by combining the benefits of the intrinsic molecular specificity of Raman spectroscopy, the sensitivity because of signal enhancing capabilities of plasmonic nanoparticles, and the precision of scanning probe microscopy. The structural differentiation of constituents based on inherent molecular information is possible even down to a few nanometer spatial resolution and consequently, nucleobases, proteins, lipids, and carbohydrates can be identified and localized in a single measurement. This has been shown in the last few years for different biological samples ranging from single DNA strand investigations to cell memb... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5051554 Sun, 17 Jul 2011 23:00:00 +0100 5051554 http://www.medworm.com/index.php?rid=5051555&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21763176%26dopt%3DAbstract Authors: Raida M Drug target deconvolution is a process where the action of a drug, a small molecule, is characterised by identifying the proteins binding the drug and initiating the biological effect. The biological relevant target has to be extracted, or deconvoluted, from a list of proteins identified in such an approach. Beside the medically desired action of the drug, the identification of other proteins binding the drug can help to identify side effects and toxicity at a very early stage of drug development. The current approach to identify the proteins binding to the drug is an affinity-enrichment based approach, where the drug molecule is immobilised to a matrix through a linker and the proteins binding to the drug are identified by proteomics. PMID: 21763176 [PubMed - as s... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5051555 Tue, 12 Jul 2011 23:00:00 +0100 5051555 http://www.medworm.com/index.php?rid=5001003&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21724447%26dopt%3DAbstract Authors: Larsson A, Jansson A, Aberg A, Nordlund P Fragment-based ligand discovery constitutes a useful strategy for the generation of high affinity ligands with suitable physico-chemical properties to serve as drug leads. There is an increasing number of generic biophysical screening strategies established with the potential for accelerating the generation of useful fragment hits. Crystal structures of these hits can subsequently be used as starting points for fragment evolution to high affinity ligands. Emerging understanding of the efficiency and operative aspects of hit generation and structural characterization in FBLD suggests that this method should be well suited for academic ligand development of chemical tools and experimental therapeutics. PMID: 21724447 [PubMed - as sup... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5001003 Thu, 30 Jun 2011 23:00:00 +0100 5001003 http://www.medworm.com/index.php?rid=5001005&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723773%26dopt%3DAbstract Authors: Mitchell W, Matsumoto S Traditional drug discovery starts by experimentally screening chemical libraries to find hit compounds that bind to protein targets, modulating their activity. Subsequent rounds of iterative chemical derivitization and rescreening are conducted to enhance the potency, selectivity, and pharmacological properties of hit compounds. Although computational docking of ligands to targets has been used to augment the empirical discovery process, its historical effectiveness has been limited because of the poor correlation of ligand dock scores and experimentally determined binding constants. Recent progress in super-computing, coupled to theoretical insights, allows the calculation of the Gibbs free energy, and therefore accurate binding constants, for usually ... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5001005 Wed, 29 Jun 2011 23:00:00 +0100 5001005 http://www.medworm.com/index.php?rid=5001004&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723774%26dopt%3DAbstract We describe in detail their identification, mechanism of action (MoA), and common features in the chemical structures. The challenges of the cell-based approach for anti-infective drug discovery are also discussed. We propose a shift from standard libraries to synthetic natural-product-like compound collections to improve the success of phenotypic lead finding and to facilitate the validation of hits. PMID: 21723774 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5001004 Wed, 29 Jun 2011 23:00:00 +0100 5001004 http://www.medworm.com/index.php?rid=5001006&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723181%26dopt%3DAbstract Authors: Espy RD, Badu-Tawiah A, Cooks RG The analysis and modification of surfaces in their native conditions can be performed using new mass spectrometric methods. Ambient ionization sources, including desorption electrospray ionization (DESI), have been implemented for the rapid analysis of unmodified biological surfaces including whole plant material, tissue sections, algae, and bacterial colonies. Recent advances have shown promise for in vivo and high-throughput clinical analysis. Additionally, the recent development of ambient ion soft landing (SL) allows polyatomic ions to be deposited onto surfaces in open air. Ambient SL offers speed, control, and flexibility for surface reactions and modification. PMID: 21723181 [PubMed - as supplied by publisher] (Source: Current Opinio... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5001006 Tue, 28 Jun 2011 23:00:00 +0100 5001006 http://www.medworm.com/index.php?rid=5001007&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21704549%26dopt%3DAbstract Authors: Fauman EB, Rai BK, Huang ES A target is druggable if it can be modulated in vivo by a drug-like molecule. The general properties of oral drugs are summarized by the 'rule of 5' which specifies parameters related to size and lipophilicity. Structure-based target druggability assessment consists of predicting ligand-binding sites on the protein that are complementary to these drug-like properties. Automated identification of ligand-binding sites can use geometrical considerations alone or include specific physicochemical properties of the protein surface. Features of a pocket's size and shape, together with measures of its hydrophobicity, are most informative in identifying suitable drug-binding pockets. The recent availability of several validation sets of druggable versus undr... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=5001007 Wed, 22 Jun 2011 23:00:00 +0100 5001007 http://www.medworm.com/index.php?rid=4956274&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21684799%26dopt%3DAbstract Authors: Kang C, Li Q Signals between a cell and its environment are often transmitted through membrane proteins; therefore, many membrane proteins, including G protein-coupled receptors (GPCRs) and ion channels, are important drug targets. Structural information about membrane proteins remains limited owing to challenges in protein expression, purification and the selection of membrane-mimicking systems that will retain protein structure and function. This review describes recent advances in solution NMR applied to the structural study of integral membrane proteins. The examples herein demonstrate that solution NMR spectroscopy will play a unique role not only in structural analysis, but also drug discovery of membrane proteins. PMID: 21684799 [PubMed - as supplied by publisher] (... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4956274 Fri, 17 Jun 2011 23:00:00 +0100 4956274 http://www.medworm.com/index.php?rid=4956273&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21684800%26dopt%3DAbstract Authors: Schmitt EK, Moore CM, Krastel P, Petersen F Natural products are evolutionarily designed and chemically distinct from most synthetic library molecules. In addition to their role as drugs, they are successfully used as molecular probes to identify disease relevant targets. Novel natural products are still routinely discovered from traditional sources through cultivation of microorganisms. Complementary approaches based on genome sequence information and subsequent annotation of biosynthetic pathways are emerging technologies. However, to be of practical use for drug discovery, these concepts must be advanced beyond their current state. PMID: 21684800 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4956273 Fri, 17 Jun 2011 23:00:00 +0100 4956273 http://www.medworm.com/index.php?rid=4956272&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21684801%26dopt%3DAbstract Authors: Mitchell W DNA sequencing has uncovered microbial secondary metabolic potential that never surfaced in fermentation based screens. Deep and cheap sequencing of a genus such as Streptomyces can rapidly expose hundreds of metabolic genes and operons. Meanwhile, synthetic biologists, in their quest to engineer advanced biofuels, are mastering metabolic engineering. Natural products, a reliable source of new therapeutic leads for many years, have fallen into disfavor with drug discoverers partly because these molecules are rarely available as pure compounds and sourcing is often problematic. The convergence of next generation sequencing and synthetic biology, along with less spectacular progress in analytic technologies such as mass spectroscopy, opens the door to the creation of ... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4956272 Fri, 17 Jun 2011 23:00:00 +0100 4956272 http://www.medworm.com/index.php?rid=4956277&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21684797%26dopt%3DAbstract Authors: de Ruiter A, Oostenbrink C In the calculation of free energies of binding for protein-ligand complexes, we distinguish endpoint methods, methods involving alchemical modifications and methods that physically displace the ligand from the protein. Most methodological advances seem to come from a clever combination of multiple existing methods to enhance the sampling or to utilize specific advantages of various approaches. The coupling parameters common in thermodynamic integration and in Hamiltonian replica exchange are for instance combined to yield replica exchange thermodynamic integration. As new methods mostly aim to improve efficiency or to attain more complete sampling, there are good prospects to understand and tackle the sampling problem better and to shift the focus to... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4956277 Thu, 16 Jun 2011 23:00:00 +0100 4956277 http://www.medworm.com/index.php?rid=4956275&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21684798%26dopt%3DAbstract Authors: Yeung BK The concept that natural products provide excellent leads for drug discovery, ultimately producing viable drugs, is a widely accepted view. Natural products embody inherent structural complexity and biological activity which often leads to new targets, pathways, or modes of action. The challenge lies in identifying quality natural product scaffolds that can ultimately result in a drug. Two recently approved drugs originating from unlikely natural product leads, ISP-1 and halichondrin B, were examples of such high quality scaffolds. In initial testing, both compounds displayed excellent in vitro potency, but more importantly were amenable to chemical optimization. This combination of unique biological activity plus the generation of structural activity relationships (S... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4956275 Thu, 16 Jun 2011 23:00:00 +0100 4956275 http://www.medworm.com/index.php?rid=4956271&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21684802%26dopt%3DAbstract Authors: Morelli X, Bourgeas R, Roche P Worldwide research efforts have driven recent pharmaceutical successes, and consequently, the emerging role of Protein-Protein Interactions (PPIs) as drug targets has finally been widely embraced by the scientific community. Inhibitors of these Protein-Protein Interactions (2P2Is or i-PPIs) are likely to represent the next generation of highly innovative drugs that will reach the market over the next decade. This review describes up-to-date knowledge on this particular chemical space, with a specific emphasis on a subset of this ensemble. We also address current structural knowledge regarding both protein-protein and protein-inhibitor complexes, that is, the 2P2I database. Finally, ligand efficiency analyses permit us to relate potency to size an... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4956271 Thu, 16 Jun 2011 23:00:00 +0100 4956271 http://www.medworm.com/index.php?rid=4956270&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21684803%26dopt%3DAbstract Authors: Brodin P, Christophe T The last decade has seen the development of automated microscopy and its adaptation for various areas of research, particularly infectious disease. Most of the high-content screening (HCS) platforms now integrate all of the following necessary steps: automated pipettes for assay miniaturization in 384-well plates, automated image acquisition and data storage and analysis. HCS was initially associated with RNA interference genetic screens for identifying host factors involved in host-pathogen interactions. More recently, both in academia and in industry, HCS has been adapted for drug discovery purposes. High-content analysis enables intracellular tracking of viral particles to profile the antiviral mechanisms of each compound. Adaptation to high-throughpu... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4956270 Thu, 16 Jun 2011 23:00:00 +0100 4956270 http://www.medworm.com/index.php?rid=4956269&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21684804%26dopt%3DAbstract Authors: Thomas GL, Johannes CW There is a paucity of chemical matter suitably poised for effective drug development. Improving the quality and efficiency of research early on in the drug discovery process has been a long standing objective for the drug industry and improvements to the accessibility and quality of compound screening decks might have a significant and positive impact. In the absence of specific molecular information that can be modeled and used predicatively we are far from identifying which small molecules are most relevant to emerging biological targets such as protein-protein interactions. Natural products have been historically successful as an entry point for drug discovery and recently screening libraries are being synthesized to emulate natural product like featu... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4956269 Thu, 16 Jun 2011 23:00:00 +0100 4956269 http://www.medworm.com/index.php?rid=4956284&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21665520%26dopt%3DAbstract Authors: Szott LM, Horbett TA Study of protein adsorption to solid surfaces continues to be substantial because of its role in cellular responses to biomaterials, interest in molecular aspects such as conformation and orientation, new methods for making protein repellent surfaces, and new application areas such as nanoparticles and microfluidics. This brief review is based only on very recent articles of particular interest to the authors, who each have worked in this area for some time. Simulations of protein interactions with surfaces and protein repellent surfaces are the only subtopics reviewed here. PMID: 21665520 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4956284 Thu, 09 Jun 2011 23:00:00 +0100 4956284 http://www.medworm.com/index.php?rid=4956280&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21665521%26dopt%3DAbstract Authors: Leach AR, Hann MM We review the concept of molecular complexity in the context of the very simple model of molecular interactions that we introduced over ten years ago. A summary is presented of efforts to validate this simple model using screening data. The relationship between the complexity model and the problem of sampling chemical space is discussed, together with the relevance of these theoretical concepts to fragment-based drug discovery. PMID: 21665521 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4956280 Thu, 09 Jun 2011 23:00:00 +0100 4956280 http://www.medworm.com/index.php?rid=4956279&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21665522%26dopt%3DAbstract Authors: Szott LM, Horbett TA PMID: 21665522 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4956279 Thu, 09 Jun 2011 23:00:00 +0100 4956279 http://www.medworm.com/index.php?rid=4956285&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21664172%26dopt%3DAbstract Authors: Fletcher JS, Vickerman JC, Winograd N Time-of-flight secondary ion mass spectrometry (ToF-SIMS) provides a method for the detection of native and exogenous compounds in biological samples on a cellular scale. Through the development of novel ion beams the amount of molecular signal available from the sample surface has been increased. Through the introduction of polyatomic ion beams, particularly C(60), ToF-SIMS can now be used to monitor molecular signals as a function of depth as the sample is eroded thus proving the ability to generate 3D molecular images. Here we describe how this new capability has led to the development of novel instrumentation for 3D molecular imaging while also highlighting the importance of sample preparation and discuss the challenges that still need... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4956285 Tue, 07 Jun 2011 23:00:00 +0100 4956285 http://www.medworm.com/index.php?rid=4907447&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21632275%26dopt%3DAbstract Authors: Casuso I, Rico F, Scheuring S For surface analysis of biological molecules, atomic force microscopy (AFM) is an appealing technique combining data acquisition under physiological conditions, for example buffer solution, room temperature and ambient pressure, and high resolution. However, a key feature of life, dynamics, could not be assessed until recently because of the slowness of conventional AFM setups. Thus, for observing bio-molecular processes, the gain of image acquisition speed signifies a key progress. Here, we review the development and recent achievements using high-speed atomic force microscopy (HS-AFM). The HS-AFM is now the only technique to assess structure and dynamics of single molecules, revealing molecular motor action and diffusion dynamics. From this imag... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4907447 Sun, 29 May 2011 23:00:00 +0100 4907447 http://www.medworm.com/index.php?rid=4907448&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21612973%26dopt%3DAbstract Authors: Touboul D, Laprévote O, Brunelle A Time-Of-Flight Secondary Ion Mass Spectrometry is compared to other mass spectrometry imaging techniques, and recent improvements of the experimental methods, driven by biological and biomedical applications, are described and discussed. This review shows that this method that can be considered as a micrometric molecular histology is particularly efficient for obtaining images of various lipid species at the surface of a tissue sample, without sample preparation, and with a routine spatial resolution of 1μm or less. PMID: 21612973 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4907448 Sun, 22 May 2011 23:00:00 +0100 4907448 http://www.medworm.com/index.php?rid=4856176&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21602093%26dopt%3DAbstract Authors: Cropp TA, McCafferty DG PMID: 21602093 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4856176 Thu, 19 May 2011 23:00:00 +0100 4856176 http://www.medworm.com/index.php?rid=4856180&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21571577%26dopt%3DAbstract Authors: Daggett KA, Sakmar TP Chemical modification of proteins has a rich history in biochemistry and chemical biology. However, studies of membrane protein function, especially in cases where functional expression is low and purification and reconstitution are not feasible, present unique challenges. Heptahelical G-protein-coupled receptors (GPCRs) are a particularly important class of cell-surface receptors that represent targets of more than a quarter of all therapeutic drugs. Understanding with chemical precision how GPCRs function in biological membranes remains a central problem in biology. Recently a number of creative strategies have been developed that allow site-specific attachment of chemical probes or tags directly on expressed receptors or on biologically active peptide ... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4856180 Thu, 12 May 2011 23:00:00 +0100 4856180 http://www.medworm.com/index.php?rid=4804297&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21536476%26dopt%3DAbstract Authors: Klenerman D, Korchev YE, Davis SJ Determining the organisation of key molecules on the surface of live cells in two dimensions and how this changes during biological processes, such as signaling, is a major challenge in cell biology and requires methods with nanoscale resolution. Recent advances in fluorescence imaging both at the diffraction limit tracking single molecules and exploiting super resolution imaging have now reached a stage where they can provide fundamentally new insights. Complementary developments in scanning ion conductance microscopy also allow the cell surface to be imaged with nanoscale resolution. The challenge now is to combine the information obtained using these different methods and on different cells to obtain a coherent view of the cell surface. In ... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4804297 Fri, 29 Apr 2011 23:00:00 +0100 4804297 http://www.medworm.com/index.php?rid=4804299&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21507706%26dopt%3DAbstract Authors: Fekner T, Chan MK The discovery of pyrrolysine not only expanded the set of the known proteinogenic amino acids but also revealed unusual features of its encoding mechanism. The engagement of a canonical stop codon and a unique aminoacyl-tRNA synthetase-tRNA pair that can be used to accommodate a broad range of unnatural amino acids while maintaining strict orthogonality in a variety of prokaryotic and eukaryotic expression systems has proven an invaluable combination. Within a few years since its properties were elucidated, the pyrrolysine translational machinery has become a popular choice for the synthesis of recombinant proteins bearing a wide variety of otherwise hard-to-introduce functional groups. It is also central to the development of new synthetic strategies that re... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4804299 Mon, 18 Apr 2011 23:00:00 +0100 4804299 http://www.medworm.com/index.php?rid=4804298&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21507707%26dopt%3DAbstract Authors: Branco MC, Sigano DM, Schneider JP As the prevalence of cancer and transmittable disease persists, the development of new and more advanced therapies remains a priority in medical research. An emerging platform for the treatment of these illnesses is the use of materials formed via peptide assembly where the bulk material itself acts as the therapeutic. Higher ordered peptide structures with defined chemistry are capable of cellular targeting, recognition, and internalization. Recent design efforts are being made to exploit the nanoscale definition of the materials formed by assembling peptides to target cancer and microbial cells and to function as vaccines. This review focuses on assembled peptide materials that actively participate in the biological processes important to c... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4804298 Sun, 17 Apr 2011 23:00:00 +0100 4804298 http://www.medworm.com/index.php?rid=4804300&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21498105%26dopt%3DAbstract Authors: Magliery TJ, Lavinder JJ, Sullivan BJ Most proteins are only barely stable, which impedes research, complicates therapeutic applications, and makes proteins susceptible to pathologically destabilizing mutations. Our ability to predict the thermodynamic consequences of even single point mutations is still surprisingly limited, and established methods of measuring stability are slow. Recent advances are bringing protein stability studies into the high-throughput realm. Some methods are based on inferential read-outs such as activity, proteolytic resistance or split-protein fragment reassembly. Other methods use miniaturization of direct measurements, such as intrinsic fluorescence, H/D exchange, cysteine reactivity, aggregation and hydrophobic dye binding (DSF). Protein engineer... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4804300 Thu, 14 Apr 2011 23:00:00 +0100 4804300 http://www.medworm.com/index.php?rid=4804304&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21489855%26dopt%3DAbstract Authors: Almonacid DE, Babbitt PC Classification of enzyme function should be quantitative, computationally accessible, and informed by sequences and structures to enable use of genomic information for functional inference and other applications. Large-scale studies have established that divergently evolved enzymes share conserved elements of structure and common mechanistic steps and that convergently evolved enzymes often converge to similar mechanisms too, suggesting that reaction mechanisms could be used to develop finer-grained functional descriptions than provided by the Enzyme Commission (EC) system currently in use. Here we describe how evolution informs these structure-function mappings and review the databases that store mechanisms of enzyme reactions along with recent develo... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4804304 Mon, 11 Apr 2011 23:00:00 +0100 4804304 http://www.medworm.com/index.php?rid=4804301&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21493122%26dopt%3DAbstract Authors: Saven JG Computational and theoretical methods are advancing protein design as a means to create and investigate proteins. Such efforts further our capacity to control, design and understand biomolecular structure, sequence and function. Herein, the focus is on some recent applications that involve using theoretical and computational methods to guide the design of protein sequence ensembles, new enzymes, proteins with novel cofactors, and membrane proteins. PMID: 21493122 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4804301 Mon, 11 Apr 2011 23:00:00 +0100 4804301 http://www.medworm.com/index.php?rid=4804303&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21489856%26dopt%3DAbstract Authors: Hong J Through the natural selection process, natural products possess a unique and vast chemical diversity and have been evolved for optimal interactions with biological macromolecules. Owing to their diversity, target affinity, and specificity, natural products have demonstrated enormous potential as modulators of biomolecular function, been an essential source for drug discovery, and provided design principles for combinatorial library development. PMID: 21489856 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4804303 Sun, 10 Apr 2011 23:00:00 +0100 4804303 http://www.medworm.com/index.php?rid=4804302&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21489857%26dopt%3DAbstract Authors: Angelini A, Heinis C The genetic encoding of polypeptides with biological display systems enables the facile generation and screening of very large combinatorial libraries of molecules. By post-translationally modifying the encoded polypeptides, chemically and structurally more diverse molecules beyond linear amino acid polymers can be generated. The first post-translational modification applied to encoded polypeptides, the oxidation of cysteine residues to form disulfide bridges, is a natural one and was used to cyclise short peptides soon after the invention of phage display. Recently a range of non-natural chemical strategies for the post-translational modification of encoded polypeptide repertoires were applied to generate optical biosensors, semisynthetic polypeptides, pe... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4804302 Sun, 10 Apr 2011 23:00:00 +0100 4804302 http://www.medworm.com/index.php?rid=4804305&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21474363%26dopt%3DAbstract Authors: Smith BA, Hecht MH The field of de novo protein design, though only two decades old, has already reached the point where designing and selecting novel proteins that are functionally active has been achieved several times. Here we review recently reported de novo functional proteins that were developed using various approaches, including rational design, computational optimization, and selection from combinatorial libraries. The functions displayed by these proteins range from metal binding to enzymatic catalysis. Some were designed for specific applications in engineering and medicine, and others provide life-sustaining functions in vivo. PMID: 21474363 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4804305 Mon, 04 Apr 2011 23:00:00 +0100 4804305 http://www.medworm.com/index.php?rid=4804307&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21470897%26dopt%3DAbstract Authors: Weber W, Fussenegger M The rapid development of synthetic biology is a paradigm of how the molecular diversity of naturally occurring gene control components can be used to design synthetic control devices and gene networks that provide precisely programmed transgene expression dynamics in space and time. Here we offer an overview on recent advances in the modular design of trigger-inducible mammalian expression devices that are either responsive by exogenous stimuli such as chemicals and physical cues or controlled by endogenous metabolites driving prosthetic circuits to treat metabolic disorders in a self-sufficient manner. Compatible genetic switches can also be assembled to synthetic gene networks that show highly complex expression dynamics such as temporally resolved ban... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4804307 Sun, 03 Apr 2011 23:00:00 +0100 4804307 http://www.medworm.com/index.php?rid=4804306&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21470898%26dopt%3DAbstract Authors: Cole MF, Gaucher EA Protein evolution relies on designing a library of sequences that capture meaningful functional diversity in a limited number of protein variants. Several approaches take advantage of the sequence space already explored through natural selection by incorporating sequence diversity available from modern genomes (and their ancestors) when designing these libraries. The success of these approaches is, partly, owing to the fact that modern sequence diversity has already been subjected to evolutionary selective forces and thus the diversity has already been deemed 'fit to survive'. Five of these approaches will be discussed in this review to highlight how protein engineers can use evolutionary sequence history/diversity of homologous proteins in unique ways to d... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4804306 Sun, 03 Apr 2011 23:00:00 +0100 4804306 http://www.medworm.com/index.php?rid=4804308&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21440485%26dopt%3DAbstract Authors: Krebs C, Bollinger JM, Booker SJ Enzymes that activate dioxygen at carboxylate-bridged non-heme diiron clusters residing within ferritin-like, four-helix-bundle protein architectures have crucial roles in, among other processes, the global carbon cycle (e.g. soluble methane monooxygenase), fatty acid biosynthesis [plant fatty acyl-acyl carrier protein (ACP) desaturases], DNA biosynthesis [the R2 or β2 subunits of class Ia ribonucleotide reductases (RNRs)], and cellular iron trafficking (ferritins). Classic studies on class Ia RNRs showed long ago how this obligatorily oxidative di-iron/O(2) chemistry can be used to activate an enzyme for even a reduction reaction, and more recent investigations of class Ib and Ic RNRs, coupled with earlier studies on dimanganese catalases, ha... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4804308 Thu, 31 Mar 2011 23:00:00 +0100 4804308 http://www.medworm.com/index.php?rid=4638148&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21435937%26dopt%3DAbstract Authors: Cronan JE, Lin S Biotin synthesis requires the C7 α,ω-dicarboxylic acid, pimelic acid. Although pimelic acid was known to be primarily synthesized by a head to tail incorporation of acetate units, the synthetic mechanism was unknown. It has recently been demonstrated that in most bacteria the biotin pimelate moiety is synthesized by a modified fatty acid synthetic pathway in which the biotin synthetic intermediates are O-methyl esters disguised to resemble the canonical intermediates of the fatty acid synthetic pathway. Upon completion of the pimelate moiety, the methyl ester is cleaved. A very restricted set of bacteria have a different pathway in which the pimelate moiety is formed by cleavage of fatty acid synthetic intermediates by BioI, a member of the cytochrome P450 f... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4638148 Tue, 22 Mar 2011 00:00:00 +0100 4638148 http://www.medworm.com/index.php?rid=4638149&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21429787%26dopt%3DAbstract Authors: Melby JO, Nard NJ, Mitchell DA With billions of years of evolution under its belt, Nature has been expanding and optimizing its biosynthetic capabilities. Chemically complex secondary metabolites continue to challenge and inspire today's most talented synthetic chemists. A brief glance at these natural products, especially the substantial structural variation within a class of compounds, clearly demonstrates that Nature has long played the role of medicinal chemist. The recent explosion in genome sequencing has expanded our appreciation of natural product space and the vastness of uncharted territory that remains. One small corner of natural product chemical space is occupied by the recently dubbed thiazole/oxazole-modified microcins (TOMMs), which are ribosomally produced pep... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4638149 Mon, 21 Mar 2011 00:00:00 +0100 4638149 http://www.medworm.com/index.php?rid=4638150&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21419690%26dopt%3DAbstract Authors: Robinson JA There is growing interest in the design of synthetic molecules that mimic the structures and functions of epitopes found on the surface of peptides and proteins. Epitope mimetics can provide valuable tools to probe complex biological processes, as well as interesting leads for drug and vaccine discovery. One application of epitope mimetics is reviewed here, focusing on mimetics of the cationic antimicrobial peptides that form part of the innate immune response to microbial and viral infection in many organisms. Mimetics of these naturally occurring peptides and proteins may be useful to explore mechanisms of antimicrobial and immunomodulatory action, and as a potential source of new antibiotics to address one of the most pressing current threats to human health. ... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4638150 Wed, 16 Mar 2011 00:00:00 +0100 4638150 http://www.medworm.com/index.php?rid=4638153&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21411359%26dopt%3DAbstract Authors: Frey PA, Outten CE PMID: 21411359 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4638153 Mon, 14 Mar 2011 00:00:00 +0100 4638153 http://www.medworm.com/index.php?rid=4638152&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21411360%26dopt%3DAbstract Authors: Barelier S, Krimm I Fragment-based screening has now become an established method for the generation of lead molecules against therapeutic targets. Fragment molecules are simple, low molecular-weight compounds with few chemical functionalities. These characteristics lead to high hit rates for fragment screening as compared to the more classical High-Throughput Screening of drug-like molecules and raise the question of the specificity of fragment molecules. This review analyzes recent outcomes of fragment screenings published in the literature, showing that the specificity of the fragments can be related to their structures and physico-chemical properties. We also discuss both the concept of privileged fragment scaffolds and the role of fragment-based screening in predicting pr... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4638152 Mon, 14 Mar 2011 00:00:00 +0100 4638152 http://www.medworm.com/index.php?rid=4638151&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21411361%26dopt%3DAbstract Authors: Glick M, Jacoby E Computational methods play an ever increasing role in lead finding. A vast repertoire of molecular design and virtual screening methods emerged in the past two decades and are today routinely used. There is increasing awareness that there is no single best computational protocol and correspondingly there is a shift recommending the combination of complementary methods. A promising trend for the application of computational methods in lead finding is to take advantage of the vast amounts of HTS (High Throughput Screening) data to allow lead assessment by detailed systems-based data analysis, especially for phenotypic screens where the identification of compound-target pairs is the primary goal. Herein, we review trends and provide examples of successful applic... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4638151 Mon, 14 Mar 2011 00:00:00 +0100 4638151 http://www.medworm.com/index.php?rid=4580046&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21393052%26dopt%3DAbstract Authors: Shepard EM, Boyd ES, Broderick JB, Peters JW Recent advances in our understanding of the mechanisms for the biosynthesis of the complex iron-sulfur (Fe-S) containing prosthetic groups associated with [FeFe]-hydrogenases and nitrogenases have revealed interesting parallels. The biosynthesis of the H-cluster ([FeFe]-hydrogenase) and the FeMo-co (nitrogenase) occurs through a coordinated process that involves the modification of Fe-S cluster precursors synthesized by the general host cell machinery (Isc/Suf). Key modifications to the Fe-S precursors are introduced by the activity of radical S-adenosylmethionine (SAM) enzymes on unique scaffold proteins. The transfer of the modified clusters to a cofactor-less structural apo-protein completes maturation. Together these features pr... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4580046 Tue, 08 Mar 2011 00:00:00 +0100 4580046 http://www.medworm.com/index.php?rid=4580047&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21362584%26dopt%3DAbstract We describe recent chemical biology studies that have utilised this structural motif for the development of potential therapeutic or diagnostic agents. The cystine knot appears to have evolved in fungi, plants and animals as a stable and adaptable framework for the display of a wide variety of bioactive peptide sequences, but is amenable to chemical or recombinant synthesis and thus has a wide range of applications in chemistry, biology and medicine. PMID: 21362584 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4580047 Sun, 27 Feb 2011 00:00:00 +0100 4580047 http://www.medworm.com/index.php?rid=4525427&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21339081%26dopt%3DAbstract Authors: Mayfield JA, Dehner CA, Dubois JL Recent progress in genetics, fed by the burst in genome sequence data, has led to the identification of a host of novel bacterial heme proteins that are now being characterized in structural and mechanistic terms. The following short review highlights very recent work with bacterial heme proteins involved in the uptake, biosynthesis, degradation, and use of heme in respiration and sensing. PMID: 21339081 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4525427 Sat, 19 Feb 2011 00:00:00 +0100 4525427 http://www.medworm.com/index.php?rid=4525429&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21334963%26dopt%3DAbstract Authors: Gotor V, Flitsch S PMID: 21334963 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4525429 Fri, 18 Feb 2011 00:00:00 +0100 4525429 http://www.medworm.com/index.php?rid=4525428&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21334964%26dopt%3DAbstract Authors: Palcic MM Glycosyltransferases are useful synthetic tools for the preparation of natural oligosaccharides, glycoconjugates and their analogues. High expression levels of recombinant enzymes have allowed their use in multi-step reactions, on mg to multi-gram scales. Since glycosyltransferases are tolerant with respect to utilizing modified donors and acceptor substrates they can be used to prepare oligosaccharide analogues and for diversification of natural products. New sources of enzymes are continually discovered as genomes are sequenced and they are annotated in the Carbohydrate Active Enzyme (CAZy) glycosyltransferase database. Glycosyltransferase mutagenesis, domain swapping and metabolic pathway engineering to change reaction specificity and product diversification are i... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4525428 Fri, 18 Feb 2011 00:00:00 +0100 4525428 http://www.medworm.com/index.php?rid=4470822&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21296609%26dopt%3DAbstract Authors: Theil EC The ferritin superfamily is composed of ancient, nanocage proteins with an internal cavity, 60% of total volume, that reversibly synthesize solid minerals of hydrated ferric oxide; the minerals are iron concentrates for cell nutrition as well as antioxidants due to ferrous and oxygen consumption during mineralization. The cages have multiple iron entry/exit channels, oxidoreductase enzyme sites, and, in eukaryotes, Fe(III)O nucleation channels with clustered exits that extend protein activity to include facilitated mineral growth. Ferritin protein cage differences include size, amino acid sequence, and location of the active sites, oxidant substrate and crystallinity of the iron mineral. Genetic regulation depends on iron and oxygen signals, which in animals includes ... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4470822 Fri, 04 Feb 2011 00:00:00 +0100 4470822 http://www.medworm.com/index.php?rid=4470823&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21292540%26dopt%3DAbstract Authors: Fleischhacker AS, Kiley PJ Iron-binding transcription factors are widespread throughout the bacterial world and to date are known to bind several types of cofactors, such as Fe(2+), heme, or iron-sulfur clusters. The known chemistry of these cofactors is exploited by transcription factors, including Fur, FNR, and NsrR, to sense molecules such as Fe(2+), gases (e.g. oxygen and nitric oxide), or reactive oxygen species. New structural data and information generated by genome-wide analysis studies have provided additional details about the mechanism and function of iron-binding transcription factors that act as sensors. PMID: 21292540 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4470823 Tue, 01 Feb 2011 00:00:00 +0100 4470823 http://www.medworm.com/index.php?rid=4470824&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21288761%26dopt%3DAbstract Authors: Subramanian P, Rodrigues AV, Ghimire-Rijal S, Stemmler TL Protein controlled iron homeostasis is essential for maintaining appropriate levels and availability of metal within cells. Recently, two iron chaperones have been discovered that direct metal within two unique pathways: (1) mitochondrial iron-sulfur (Fe-S) cluster assembly and (2) within the ferritin iron storage system. Although structural and functional details describing how these iron chaperones operate are emerging, both share similar iron binding affinities and metal-ligand site structures that enable them to bind and release Fe(2+) to specific protein partners. Molecular details related to iron binding and delivery by these chaperones will be explored within this review. PMID: 21288761 [PubMed - as supplied ... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4470824 Mon, 31 Jan 2011 00:00:00 +0100 4470824 http://www.medworm.com/index.php?rid=4470826&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21282071%26dopt%3DAbstract Authors: Dorrestein PC, Carroll KS PMID: 21282071 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4470826 Sat, 29 Jan 2011 00:00:00 +0100 4470826 http://www.medworm.com/index.php?rid=4470825&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21282072%26dopt%3DAbstract Authors: Lindahl PA, Holmes-Hampton GP In living systems, iron is found in many different structures, including Fe/S clusters, hemes and nonheme centers, and magnetically interacting aggregates. Understanding Fe metabolism and trafficking will require biophysical spectroscopic tools that can evaluate the types of Fe centers within entire cells and isolated organelles. Mössbauer spectroscopy will play an important role in such analyses, as it has perhaps the best combination of resolution, sensitivity, coverage, and quantifying abilities. Other spectroscopic techniques, with particular strengths, will be used in combination with Mössbauer, and results will be integrated to assess the 'ironome' of such complex samples. This integrative biophysical approach is illustrated by a discussio... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4470825 Sat, 29 Jan 2011 00:00:00 +0100 4470825 http://www.medworm.com/index.php?rid=4470827&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21277822%26dopt%3DAbstract Authors: Braun V, Hantke K Bacteria are confronted with a low availability of iron owing to its insolubility in the Fe(3+) form or its being bound to host proteins. The bacteria cope with the iron deficiency by using host heme or siderophores synthesized by themselves or other microbes. In contrast to most other nutrients, iron compounds are tightly bound to proteins at the cell surfaces, from which they are further translocated by highly specific proteins across the cell wall of gram-positive bacteria and the outer membrane of gram-negative bacteria. Once heme and iron siderophores arrive at the cytoplasmic membrane, they are taken up across the cytoplasmic membrane by ABC transporters. Here we present an outline of bacterial heme and iron siderophore transport exemplified by a few se... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4470827 Fri, 28 Jan 2011 00:00:00 +0100 4470827 http://www.medworm.com/index.php?rid=4470828&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21276746%26dopt%3DAbstract Authors: Díaz-Rodríguez A, Davis BG Enzymes are able to perform a multitude of chemical and biochemical transformations with efficiencies that are typically unrivalled by chemical catalysts. However, these evolved systems may lack breadth or utility in other non-natural applications. Altering enzyme and protein scaffolds through covalent modification can expand the usefulness of native biocatalysts not only for synthetic application but also for therapeutic use. This review summarizes recent developments in the field of chemical modification of enzymes and how they can be applied to synthesis and biological research. PMID: 21276746 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4470828 Wed, 26 Jan 2011 00:00:00 +0100 4470828 http://www.medworm.com/index.php?rid=4337637&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21216656%26dopt%3DAbstract Authors: Stubbe J, Cotruvo JA Ribonucleotide reductases (RNRs) convert nucleotides to deoxynucleotides in all organisms. Activity of the class Ia and Ib RNRs requires a stable tyrosyl radical (Y), which can be generated by the reaction of O(2) with a diferrous cluster on the β subunit to form active diferric-Y cofactor. Recent experiments have demonstrated, however, that in vivo the class Ib RNR contains an active dimanganese(III)-Y cofactor. The similar metal binding sites of the class Ia and Ib RNRs, their ability to bind both Mn(II) and Fe(II), and the activity of the class Ib RNR with both diferric-Y and dimanganese(III)-Y cofactors raise the intriguing question of how the cell prevents mismetallation of these essential enzymes. The presence of the class Ib RNR in numerous pathoge... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4337637 Fri, 07 Jan 2011 00:00:00 +0100 4337637 http://www.medworm.com/index.php?rid=4337636&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21216657%26dopt%3DAbstract This article summarizes progress in quantitative redox proteomics to develop such maps. PMID: 21216657 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4337636 Fri, 07 Jan 2011 00:00:00 +0100 4337636 http://www.medworm.com/index.php?rid=4337639&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21195017%26dopt%3DAbstract Authors: Hur W, Gray NS Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that regulates Antioxidant Response Element (ARE)-mediated transcription of a plethora of antioxidant and protective genes to counteract the harmful effects of reactive oxygen species or environmental carcinogens. Studies have demonstrated that pre-emptive activation of the Nrf2-ARE pathway reinforces the cellular defense mechanism against oxidative stress and leads to protection in a variety of disease models. Non-carcinogenic ARE inducers have been identified from a variety of chemical classes that enhance the transcriptional activity of Nrf2 through S-alkylation of reactive cysteines within the cellular redox sensor protein Keap1 (Kelch-like ECH associated protein 1). Here we review the curre... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4337639 Wed, 29 Dec 2010 00:00:00 +0100 4337639 http://www.medworm.com/index.php?rid=4337638&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21195018%26dopt%3DAbstract Authors: Nestl BM, Nebel BA, Hauer B In recent years, several procedures have been reported for the development of biocatalytic processes. This review focuses on selected examples integrating biocatalysts into a variety of industrially interesting processes ranging from the manufacture of smaller, chiral speciality chemicals to the synthesis of more complex pharmaceutical intermediates. The use of rational protein design, multistep processes and de novo design of enzyme catalysts for the stereocontrolled preparation of important target structures is discussed. PMID: 21195018 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4337638 Wed, 29 Dec 2010 00:00:00 +0100 4337638 http://www.medworm.com/index.php?rid=4337640&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21185770%26dopt%3DAbstract Authors: Brustad EM, Arnold FH Developing technologies such as unnatural amino acid mutagenesis, non-natural cofactor engineering, and computational design are generating proteins with novel functions; these proteins, however, often do not reach performance targets and would benefit from further optimization. Evolutionary methods can complement these approaches: recent work combining unnatural amino acid mutagenesis and phage selection has created useful proteins of novel composition. Weak initial activity in a computationally designed enzyme has been improved by iterative rounds of mutagenesis and screening. A marriage of ingenuity and evolution will expand the scope of protein function well beyond Mother Nature's designs. PMID: 21185770 [PubMed - as supplied by publisher] (Source... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4337640 Thu, 23 Dec 2010 00:00:00 +0100 4337640 http://www.medworm.com/index.php?rid=4337641&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21159543%26dopt%3DAbstract Authors: Roach PL The radical SAM superfamily of enzymes catalyzes a broad spectrum of biotransformations by employing a common obligate intermediate, the 5'-deoxyadenosyl radical (DOA). Radical formation occurs via the reductive cleavage of S-adenosylmethionine (SAM or AdoMet). The resultant highly reactive primary radical is a potent oxidant that enables the functionalization of relatively inert substrates, including unactivated C-H bonds. The reactions initiated by the DOA are breathtaking in their efficiency, elegance and in many cases, the complexity of the biotransformation achieved. This review describes the common features shared by enzymes that generate the DOA and the intriguing variations or modifications that have recently been reported. The review also highlights selected ... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4337641 Mon, 13 Dec 2010 00:00:00 +0100 4337641 http://www.medworm.com/index.php?rid=4337642&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21145278%26dopt%3DAbstract Authors: Grogan G The remarkable chemical reactivity and substrate range displayed by cytochromes P450 (P450s) renders them attractive as potential catalysts for a host of challenging chemical reactions in industry. The opportunities afforded by these biocatalysts are increased by the availability of greater diversity provided by the genomic resource and the variant libraries of well-known P450s produced by rational and random engineering techniques. The exploitation of this enormous diversity will require novel tools in screening, to identify enzyme reactions of interest, and also in the enabling of these valuable activities through protein engineering and bioprocess optimisation. PMID: 21145278 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4337642 Tue, 07 Dec 2010 00:00:00 +0100 4337642 http://www.medworm.com/index.php?rid=4251043&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21131229%26dopt%3DAbstract Authors: Turner NJ Ammonia lyases catalyse the reversible addition of ammonia to cinnamic acid (1: R=H) and p-hydroxycinnamic (1: R=OH) to generate l-phenylalanine (2: R=H) and l-tyrosine (2: R=OH) respectively (Figure 1a). Both phenylalanine ammonia lyase (PAL) and tyrosine ammonia lyase (TAL) are widely distributed in plants, fungi and prokaryotes. Recently there has been interest in the use of these enzymes for the synthesis of a broader range of l-arylalanines. Aminomutases catalyse a related reaction, namely the interconversion of α-amino acids to β-amino acids (Figure 1b). In the case of l-phenylalanine, this reaction is catalysed by phenylalanine aminomutase (PAM) and proceeds stereospecifically via the intermediate cinnamic acid to generate β-Phe 3. Ammonia lyases and aminom... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4251043 Fri, 03 Dec 2010 00:00:00 +0100 4251043 http://www.medworm.com/index.php?rid=4251044&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21130680%26dopt%3DAbstract This article reviews the current, targeted proteomic strategies that are available to detect and quantify cysteine oxidation. A number of indirect methods have been developed to monitor changes in the redox state of cysteines, with the majority relying on the loss of reactivity with thiol-modifying reagents or restoration of labeling by reducing agents. Recent advances in chemical biology allow for the direct detection of specific cysteine oxoforms based on their distinct chemical attributes. In addition, new chemical reporters of cysteine oxidation have enabled in situ detection of labile modifications and improved proteomic analysis of redox-regulated proteins. Progress in the field of redox proteomics should advance our knowledge of regulatory mechanisms that involve oxidation of cystei... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4251044 Thu, 02 Dec 2010 00:00:00 +0100 4251044 http://www.medworm.com/index.php?rid=4251049&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21130020%26dopt%3DAbstract Authors: Chouchani ET, James AM, Fearnley IM, Lilley KS, Murphy MP Protein cysteine residues are central to redox signaling and to protection against oxidative damage through their interactions with reactive oxygen and nitrogen species, and electrophiles. Although there is considerable evidence for a functional role for cysteine modifications, the identity and physiological significance of most protein thiol alterations are unknown. One way to identify candidate proteins involved in these processes is to utilize the proteomic methodologies that have been developed in recent years for the identification of proteins that undergo cysteine modification in response to redox signals or oxidative damage. These tools have proven effective in uncovering novel protein targets of redox modificati... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4251049 Wed, 01 Dec 2010 00:00:00 +0100 4251049 http://www.medworm.com/index.php?rid=4251048&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21130021%26dopt%3DAbstract Authors: Shi W, Chance MR About one-third of all proteins are associated with a metal. Metalloproteomics is defined as the structural and functional characterization of metalloproteins on a genome-wide scale. The methodologies utilized in metalloproteomics, including both forward (bottom-up) and reverse (top-down) technologies, to provide information on the identity, quantity, and function of metalloproteins are discussed. Important techniques frequently employed in metalloproteomics include classical proteomic tools such as mass spectrometry and 2D gels, immobilized-metal affinity chromatography, bioinformatic sequence analysis and homology modeling, X-ray absorption spectroscopy and other synchrotron radiation based tools. Combinative applications of these techniques provide a powerf... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4251048 Wed, 01 Dec 2010 00:00:00 +0100 4251048 http://www.medworm.com/index.php?rid=4251047&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21130022%26dopt%3DAbstract Authors: Kung Y, Drennan CL Ni-Fe containing enzymes are involved in the biological utilization of carbon monoxide, carbon dioxide, and hydrogen. Interest in these enzymes has increased in recent years due to hydrogen fuel initiatives and concerns over development of new methods for CO(2) sequestration. One Ni-Fe enzyme called carbon monoxide dehydrogenase (CODH) is a key player in the global carbon cycle and carries out the interconversion of the environmental pollutant CO and the greenhouse gas CO(2). The Ni-Fe center responsible for this important chemistry, the C-cluster, has been the source of much controversy, but several recent structural studies have helped to direct the field toward a unifying mechanism. Here we summarize the current state of understanding of this fascinating ... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4251047 Wed, 01 Dec 2010 00:00:00 +0100 4251047 http://www.medworm.com/index.php?rid=4251046&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21130023%26dopt%3DAbstract Authors: Thamsen M, Jakob U Redox-regulated proteins play fundamentally important roles not only during the defense of organisms against oxidative stress conditions but also as targets of cellular signaling events. This realization has spurred the development of proteomic techniques geared towards characterizing the redoxome; proteins with highly reactive cysteine residues, whose thiol oxidation state controls the function of the proteins, and by extension, the pathways they are part of. We will here summarize the most recent advances made in the field of redox proteomic analysis, aimed to elucidate the cellular redox networks that appear to control prokaryotic and eukaryotic organisms. PMID: 21130023 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4251046 Wed, 01 Dec 2010 00:00:00 +0100 4251046 http://www.medworm.com/index.php?rid=4251045&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21130024%26dopt%3DAbstract Authors: Schrittwieser JH, Sattler J, Resch V, Mutti FG, Kroutil W The combination of an oxidation and a reduction in a cascade allows performing transformations in a very economic and efficient fashion. The challenge is how to combine an oxidation with a reduction in one pot, either by running the two reactions simultaneously or in a stepwise fashion without isolation of intermediates. The broader availability of various redox enzymes nowadays has triggered the recent investigation of various oxidation-reduction cascades. PMID: 21130024 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4251045 Wed, 01 Dec 2010 00:00:00 +0100 4251045 http://www.medworm.com/index.php?rid=4218135&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21115265%26dopt%3DAbstract Authors: Bommarius AS, Blum JK, Abrahamson MJ Recent advances in the development of both experimental and computational protein engineering tools have enabled a number of further successes in the development of biocatalysts ready for large-scale applications. Key tools are first, the targeting of libraries, leading to far smaller but more useful libraries than in the past, second, the combination of structural, mechanistic, and sequence-based knowledge often based on prior successful cases, and third, the advent of structurally based algorithms allowing the design of novel functions. Based on these tools, a number of improved biocatalysts for pharmaceutical applications have been presented, such as an (R)-transaminase for the synthesis of active pharmaceutical ingredients (APIs) of sit... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4218135 Sat, 27 Nov 2010 00:00:00 +0100 4218135 http://www.medworm.com/index.php?rid=4218140&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21112808%26dopt%3DAbstract Authors: Domínguez de María P, Maugeri Z Ionic liquids (ILs) have been extensively assessed in biotransformations with different purposes, for example, non-conventional (co-)solvents, performance additives, coating agents for immobilizing/stabilizing enzymes, and IL-membrane-based processes. Fuelled by their premature labelling as 'green solvents', academic research has flourished. However, in recent years environmental aspects related to ILs have been strongly addressed, stating that many ILs commonly used cannot be regarded as 'green derivatives'. Likewise, ILs costs are still a barrier for practical uses. Attempting to combine sustainability with the promising added-values of ILs, the third generation of ILs is currently under development. Likewise, deep-eutectic-solvents (DESs) a... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4218140 Fri, 26 Nov 2010 00:00:00 +0100 4218140 http://www.medworm.com/index.php?rid=4218144&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21112236%26dopt%3DAbstract Authors: Francis MB, Carrico I PMID: 21112236 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4218144 Thu, 25 Nov 2010 00:00:00 +0100 4218144 http://www.medworm.com/index.php?rid=4218158&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21111667%26dopt%3DAbstract Authors: Winter JM, Behnken S, Hertweck C The massive surge in genome sequencing projects has opened our eyes to the overlooked biosynthetic potential and metabolic diversity of microorganisms. While traditional approaches have been successful at identifying many useful therapeutic agents from these organisms, new tactics are needed in order to exploit their true biosynthetic potential. Several genomics-inspired strategies have been successful in unveiling new metabolites that were overlooked under standard fermentation and detection conditions. In addition, genome sequences have given us valuable insight for genetically engineering biosynthesis gene clusters that remain silent or are poorly expressed in the absence of a specific trigger. As more genome sequences are becoming available... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4218158 Wed, 24 Nov 2010 00:00:00 +0100 4218158 http://www.medworm.com/index.php?rid=4218154&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21111668%26dopt%3DAbstract Authors: Davies J There is a dire need for new antibiotics; commercial discovery programs have essentially dried up and there is talk of 'a return to the pre-antibiotic era'. Natural products are an inexhaustible source of bioactive compounds (antibiotics among them), and recent technical advances such as DNA sequencing and bioinformatics offer new approaches to small molecule discovery. Given that nucleotide sequence studies of actinomycetes genomes reveal the presence of 20 or more pathways for the synthesis of bioactive compounds, 'mining' these sequences offers the potential of expanding the repertoire of antibiotics and other drugs. Combined with advanced chemical separation and characterization techniques, the construction of large chemically diverse libraries of bioactive compou... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4218154 Wed, 24 Nov 2010 00:00:00 +0100 4218154 http://www.medworm.com/index.php?rid=4218150&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21111669%26dopt%3DAbstract Authors: Chiang YM, Chang SL, Oakley BR, Wang CC Secondary metabolites from microorganisms have a broad spectrum of applications, particularly in therapeutics. The growing number of sequenced microbial genomes has revealed a remarkably large number of natural product biosynthetic clusters for which the products are still unknown. These cryptic clusters are potentially a treasure house of medically useful compounds. The recent development of new methodologies has made it possible to begin unlock this treasure house, to discover new natural products and to determine their biosynthesis pathways. This review will highlight some of the most recent strategies to activate silent biosynthetic gene clusters and to elucidate their corresponding products and pathways. PMID: 21111669 [PubMed -... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4218150 Wed, 24 Nov 2010 00:00:00 +0100 4218150 http://www.medworm.com/index.php?rid=4218162&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21095156%26dopt%3DAbstract Authors: Velásquez JE, van der Donk WA In recent years, the number of known peptide natural products that are synthesized via the ribosomal pathway has rapidly grown. Taking advantage of sequence homology among genes encoding precursor peptides or biosynthetic proteins, in silico mining of genomes combined with molecular biology approaches has guided the discovery of a large number of new ribosomal natural products, including lantipeptides, cyanobactins, linear thiazole/oxazole-containing peptides, microviridins, lasso peptides, amatoxins, cyclotides, and conopeptides. In this review, we describe the strategies used for the identification of these ribosomally synthesized and posttranslationally modified peptides (RiPPs) and the structures of newly identified compounds. The increasing ... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4218162 Sat, 20 Nov 2010 00:00:00 +0100 4218162 http://www.medworm.com/index.php?rid=4218165&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21093351%26dopt%3DAbstract Authors: Ho CH, Piotrowski J, Dixon SJ, Baryshnikova A, Costanzo M, Boone C Genome sequencing projects have revealed thousands of suspected genes, challenging researchers to develop efficient large-scale functional analysis methodologies. Determining the function of a gene product generally requires a means to alter its function. Genetically tractable model organisms have been widely exploited for the isolation and characterization of activating and inactivating mutations in genes encoding proteins of interest. Chemical genetics represents a complementary approach involving the use of small molecules capable of either inactivating or activating their targets. Saccharomyces cerevisiae has been an important test bed for the development and application of chemical genomic assays aimed at ... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4218165 Wed, 17 Nov 2010 00:00:00 +0100 4218165 http://www.medworm.com/index.php?rid=4185176&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21087892%26dopt%3DAbstract Authors: Yang JY, Karr JR, Watrous JD, Dorrestein PC The microbiome is an abundance of microorganisms within a host (e.g. human microbiome). These microorganisms produce small molecules and metabolites that have been shown to affect and dictate the physiology of an individual. Functional knowledge of these molecules, often produced for communication or defense, will reveal the interplay between microbes and host in health and disease. The vast diversity in structure and function of microbiome-associated small molecules necessitate tools that will utilize multiple '-omics' strategies to understand the interactions within the human microbiome. This review discusses the importance of these investigations and the integration of current '-omics' technologies with tools established in natura... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4185176 Wed, 17 Nov 2010 00:00:00 +0100 4185176 http://www.medworm.com/index.php?rid=4185175&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21087893%26dopt%3DAbstract Authors: Seth D, Stamler JS Cell signaling is a complex and highly regulated process. Post-translational modifications of proteins serve to sense and transduce cellular signals in a precisely coordinated manner. It is increasingly recognized that protein S-nitrosylation, the addition of a nitric oxide group to cysteine thiols, serves an important role in a wide range of signaling pathways. In spite of the large number of SNO-proteins now identified (∼1000), the observed specificity of S-nitrosylation in terms of target proteins and specific cysteines within modified proteins is incompletely understood. Here we review the progress made in S-nitrosylation detection methods that have facilitated the study of the SNO-proteome under physiological and pathophysiological conditions, and som... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4185175 Wed, 17 Nov 2010 00:00:00 +0100 4185175 http://www.medworm.com/index.php?rid=4185174&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21087894%26dopt%3DAbstract Authors: Meier JL, Burkart MD Polyketides and non-ribosomal peptides are in a class of natural products important both as drug sources and as dangerous toxins and virulence factors. While studies over the last two decades have provided substantial characterization of the modular synthases that produce these compounds at the genetic level, their understanding at the protein level is much less understood. New proteomic platforms called an orthogonal active site identification system (OASIS) and proteomic interrogation of secondary metabolism (PrISM) have been developed to identify and quantify natural product synthase enzymes. Reviewed here, these tools offer the means to discover and analyze modular synthetic pathways that are limited by genetic techniques, opening the tools of contempo... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4185174 Wed, 17 Nov 2010 00:00:00 +0100 4185174 http://www.medworm.com/index.php?rid=4185177&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21075673%26dopt%3DAbstract Authors: Chalker JM, Davis BG The ability to alter protein structure by site-directed mutagenesis has revolutionized biochemical research. Controlled mutations at the DNA level, before protein translation, are now routine. These techniques allow specific, high fidelity interconversion largely between 20 natural, proteinogenic amino acids. Nonetheless, there is a need to incorporate other amino acids, both natural and unnatural, that are not accessible using standard site-directed mutagenesis and expression systems. Post-translational chemistry offers access to these side chains. Nearly half a century ago, the idea of a 'chemical mutation' was proposed and the interconversion between amino acid side chains was demonstrated on select proteins. In these isolated examples, a powerful proof... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4185177 Fri, 12 Nov 2010 00:00:00 +0100 4185177 http://www.medworm.com/index.php?rid=4185179&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21075043%26dopt%3DAbstract Authors: Tew KD, Townsend DM Redox homeostasis is frequently dysregulated in human disease, particularly cancer. Recent and ongoing efforts seek to validate and extend this platform for the discovery/development of anticancer drugs. As the primary source of cellular redox buffer, thiols (in particular glutathione) have been therapeutically targeted in cancer treatment, myeloproliferation, hematopoietic progenitor cell mobilization and immune response. A number of 'redox modulating' drugs have been, or are, under development and the pipeline seems viable. Moreover, S-glutathionylation is a protein post-translational modification that influences a number of critical cell pathways and in the medium term, defining the 'glutathionome' has the possibility to provide opportunities for target ... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4185179 Thu, 11 Nov 2010 00:00:00 +0100 4185179 http://www.medworm.com/index.php?rid=4185178&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21075044%26dopt%3DAbstract Authors: Johnston PA Redox cycling compounds (RCCs) generate μM concentrations of hydrogen peroxide (H(2)O(2)) in the presence of strong reducing agents, common buffer components used to maintain the catalytic activity and/or folding of target proteins for high throughput screening (HTS) assays. H(2)O(2) generated by RCCs can indirectly inhibit the catalytic activity of proteins by oxidizing accessible cysteine, tryptophan, methionine, histidine, or selenocysteine residues, and indeed several important classes of protein targets are susceptible to H(2)O(2)-mediated inactivation; protein tyrosine phosphatases, cysteine proteases, and metalloenzymes. The main sources of H(2)O(2) in cells are the Nox enzyme/SOD systems, peroxisome metabolism, and the autoxidation of reactive chemicals by... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4185178 Thu, 11 Nov 2010 00:00:00 +0100 4185178 http://www.medworm.com/index.php?rid=4166229&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21071259%26dopt%3DAbstract Authors: Johnson JA, Lu YY, Van Deventer JA, Tirrell DA Residue-specific incorporation of non-canonical amino acids into proteins allows facile alteration and enhancement of protein properties. In this review, we describe recent technical developments and applications of residue-specific incorporation to problems ranging from elucidation of biochemical mechanisms to engineering of protein-based biomaterials. We hope to inform the reader of the ease and broad utility of residue-specific non-canonical amino acid incorporation with the goal of inspiring investigators outside the field to consider applying this tool to their own research. PMID: 21071259 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4166229 Tue, 09 Nov 2010 00:00:00 +0100 4166229 http://www.medworm.com/index.php?rid=4166228&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21071260%26dopt%3DAbstract Authors: Grover GN, Maynard HD Protein-polymer conjugates are of interest to researchers in diverse fields. Attachment of polymers to proteins results in improved pharmacokinetics, which is important in medicine. From an engineering standpoint, conjugates are exciting because they exhibit properties of both the biomolecules and synthetic polymers. This allows the activity of the protein to be altered or tuned, anchoring to surfaces, and supramolecular self-assembly. Thus, there is broad interest in straightforward synthetic methods to prepare protein-polymer conjugates. Controlled radical polymerization (CRP) techniques have emerged as excellent strategies to make conjugates because the resulting polymers have narrow molecular weight distributions, targeted molecular weights, and attac... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4166228 Tue, 09 Nov 2010 00:00:00 +0100 4166228 http://www.medworm.com/index.php?rid=4166227&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21071261%26dopt%3DAbstract Authors: Forseth RR, Schroeder FC NMR spectroscopy as a particularly information-rich method offers unique opportunities for improving the structural and functional characterization of metabolomes, which will be essential for advancing the understanding of many biological processes. Whereas traditionally NMR spectroscopy was mostly relegated to the characterization of pure compounds, the past few years have seen a surge of interest in using NMR-spectroscopic techniques for characterizing complex metabolite mixtures. Development of new methods was motivated partly by the realization that using NMR for the analysis of metabolite mixtures can help identify otherwise inaccessible small molecules, for example compounds that are prone to chemical decomposition and thus cannot be isolated. Fu... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4166227 Tue, 09 Nov 2010 00:00:00 +0100 4166227 http://www.medworm.com/index.php?rid=4139592&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21036656%26dopt%3DAbstract Authors: Koudelka KJ, Manchester M The search for novel molecular materials has focused on viruses as natural nanomaterials. Historically studied for their effects as pathogens, recent advances have incorporated viruses as substrates for chemical modification, materials development, and therapeutic design. Here we will discuss recent advances in chemical strategies for modifying viruses, and the applications of these technologies. PMID: 21036656 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4139592 Fri, 29 Oct 2010 00:00:00 +0100 4139592 http://www.medworm.com/index.php?rid=4139591&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21036657%26dopt%3DAbstract Authors: Wang H, Xian M Nitric oxide (NO) is a cell-signaling molecule involved in a number of physiological and pathophysiological processes. Modification of cysteine residues by NO (or NO metabolites), that is S-nitrosation, changes the function of a broad spectrum of proteins. This reaction represents an important post-translational modification that transduces NO-dependent signals. However, the detection and quantification of S-nitrosation in biological samples remain a challenge mainly because of the lability of S-nitrosation products: S-nitrosothiols (SNO). In this review we summarize recent developments of the methods to detect S-nitrosation. Our focus is on the methods which can be used to directly conjugate the site(s) of S-nitrosation. PMID: 21036657 [PubMed - as supplied... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4139591 Fri, 29 Oct 2010 00:00:00 +0100 4139591 http://www.medworm.com/index.php?rid=4139593&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21035376%26dopt%3DAbstract Authors: Rana S, Yeh YC, Rotello VM Covalent and non-covalent conjugation of proteins to nanoparticles provides access to functional hybrid systems with applications in biotechnology, medicine, and catalysis. The creation of effective conjugates requires the retention of protein structure and function, a challenging task. In this review we discuss successes, challenges and opportunities in the area of protein-nanoparticle bioconjugation. PMID: 21035376 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4139593 Wed, 27 Oct 2010 00:00:00 +0100 4139593 http://www.medworm.com/index.php?rid=4123340&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21030291%26dopt%3DAbstract Authors: Rabuka D In the past decade, numerous chemical technologies have been developed to allow the site-specific post-translational modification of proteins. Traditionally covalent chemical protein modification has been accomplished by the attachment of synthetic groups to nucleophilic amino acids on protein surfaces. These chemistries, however, are rarely sufficiently selective to distinguish one residue within a literal sea of chemical functionality. One solution to this problem is to introduce a unique chemical handle into the target protein that is orthogonal to the remainder of the proteome. In practice, this handle can be a novel peptide sequence, which forms a 'tag' that is selectively and irreversibly modified by enzymes. Furthermore, if the enzymes can tolerate substrate an... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4123340 Tue, 26 Oct 2010 00:00:00 +0100 4123340 http://www.medworm.com/index.php?rid=4088323&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20965773%26dopt%3DAbstract Authors: Focke PJ, Vailyaveetil FI Expressed protein ligation (EPL) is a semisynthetic technique for the chemoselective ligation of a synthetic peptide to a recombinant peptide that results in a native peptide bond at the ligation site. EPL therefore allows us to engineer proteins with chemically defined, site-specific modifications. While EPL has been used mainly in investigations of soluble proteins, in recent years it has been increasingly used in investigations of integral membrane proteins. These include studies on the KcsA K(+) channel, the non-selective cation channel NaK, and the porin OmpF. These studies are discussed in this review. PMID: 20965773 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4088323 Mon, 18 Oct 2010 23:00:00 +0100 4088323 http://www.medworm.com/index.php?rid=4088324&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20952245%26dopt%3DAbstract Authors: Day JJ, Marquez BV, Beck HE, Aweda TA, Gawande PD, Meares CF Notable new applications of antibodies for imaging involve genetically extracting the essential molecular recognition properties of an antibody, and in some cases enhancing them by mutation, before protein expression. The classic paradigm of intravenous administration of a labeled antibody to image not only its target but also its metabolism can be improved on. Protocols involving molecular targeting with an engineered unlabeled protein derived from an antibody, followed by capture of a small probe molecule that provides a signal, are being developed to a high level of utility. This is accompanied by new strategies for probe capture such as irreversible binding, incorporation of engineered enzyme active sites, and an... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4088324 Thu, 14 Oct 2010 23:00:00 +0100 4088324 http://www.medworm.com/index.php?rid=4042923&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20888286%26dopt%3DAbstract Authors: Lee SE, Lee LP This review focuses on the recent developments in nanoplasmonic optical gene regulations. Types of nanoplasmonic carriers and DNA/RNA cargo are described. Strategies to liberate cargo from their carriers using NIR are reviewed. Nanoplasmonic optical gene switches enable on-demand and systematic silencing of endogenous intracellular genes. In addition to inhibitory effects, exogenous foreign genes are also introduced and expressed on-demand using nanoplasmonic optical switches. The magnitude and timing of genetic activities can therefore be systematically controlled on-demand remotely. Equipped with new nanoplasmonic optics to directly probe the intracellular space, quantitative approaches should capture many dynamic activities within living systems that were oth... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4042923 Tue, 28 Sep 2010 23:00:00 +0100 4042923 http://www.medworm.com/index.php?rid=4003503&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20870450%26dopt%3DAbstract Authors: O'Brien PJ, Hollfelder F PMID: 20870450 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4003503 Thu, 23 Sep 2010 23:00:00 +0100 4003503 http://www.medworm.com/index.php?rid=4003863&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20869904%26dopt%3DAbstract Authors: Kintses B, van Vliet LD, Devenish SR, Hollfelder F Miniaturization of the classical test tube to picoliter dimensions is possible in monodisperse water-in-oil droplets that are generated in microfluidic devices. The establishment of standard unit operations for droplet handling and the ability to carry out experiments with DNA, proteins, cells and organisms provides the basis for the design of more complex workflows to address biological challenges. The emerging experimental format makes possible a quantitative readout for large numbers of experiments with a precision comparable to the macroscopic scale. Directed evolution, diagnostics and compound screening are areas in which the first steps are being taken toward the long-term goal of transforming the way we design and carry... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4003863 Wed, 22 Sep 2010 23:00:00 +0100 4003863 http://www.medworm.com/index.php?rid=4003774&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20869905%26dopt%3DAbstract Authors: Lo PK, Metera KL, Sleiman HF A current challenge in nanoscience is to achieve controlled organization in three-dimensions, to provide tools for biophysics, molecular sensors, enzymatic cascades, drug delivery, tissue engineering, and device fabrication. DNA displays some of the most predictable and programmable interactions of any molecule, natural or synthetic. As a result, 3D-DNA nanostructures have emerged as promising tools for biology and materials science. In this review, strategies for 3D-DNA assembly are discussed. DNA cages, nanotubes, dendritic networks, and crystals are formed, with deliberate variation of their size, shape, persistence length, and porosities. They can exhibit dynamic character, allowing their selective switching with external stimuli. They can enca... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4003774 Wed, 22 Sep 2010 23:00:00 +0100 4003774 http://www.medworm.com/index.php?rid=4003575&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20869906%26dopt%3DAbstract Authors: Demello AJ, Woolley AT PMID: 20869906 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4003575 Wed, 22 Sep 2010 23:00:00 +0100 4003575 http://www.medworm.com/index.php?rid=4003927&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20863741%26dopt%3DAbstract Authors: Anslyn EV, Rotello VM PMID: 20863741 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=4003927 Sun, 19 Sep 2010 23:00:00 +0100 4003927 http://www.medworm.com/index.php?rid=3971018&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20833099%26dopt%3DAbstract Authors: Narlikar GJ ATP-dependent chromatin remodeling motors play fundamental roles in nuclear processes by regulating access to DNA. Yet compared to other cellular motors less is known about how these motors couple the energy of ATP to alter their substrates. Here we use recent studies on a key chromatin remodeling motor from the ISWI class, human ACF and its yeast counterpart, ISW2, to propose a model for how these motors use ATP to read structural cues presented by nucleosomal substrates. Substantial earlier work has shown that ACF activity is strongly regulated by the length of the DNA flanking a nucleosome as well as by the histone H4 tail. Recent bulk and single-molecule studies of human ACF suggest that this complex functions as a dimeric motor. These studies, together with st... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=3971018 Wed, 08 Sep 2010 23:00:00 +0100 3971018 http://www.medworm.com/index.php?rid=3971020&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20832351%26dopt%3DAbstract Authors: Vendruscolo M Although disordered proteins are able to carry out a variety of different functions, particularly those involved in signalling and regulation, they have been observed to perform catalysis only in a small number of cases. The presence of structural disorder is indeed expected to be poorly compatible with enzymatic catalysis, which requires a well-organised environment in the active site of the enzyme in order to facilitate the formation of the transition state of the chemical reaction to be catalysed. Despite this stringent requirement, current evidence suggests that certain partially disordered proteins could be catalytically active by becoming structured in the regions of their active sites, even if their overall states retain a significant degree of conformatio... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=3971020 Tue, 07 Sep 2010 23:00:00 +0100 3971020 http://www.medworm.com/index.php?rid=3971019&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20832352%26dopt%3DAbstract Authors: Wlodkowic D, Cooper JM Despite over 2 million papers published on cancer so far, malignancy still remains a puzzlingly complex disease with overall low survival rates. Expanding our knowledge of the molecular mechanisms of malignancy and of resistance to therapy is crucial in guiding the successful design of anti-cancer drugs and new point-of-care diagnostics. The up-and-coming microfluidic Lab-on-a-Chip (LOC) technology and micro-total analysis systems (μTAS) are arguably the most promising platforms to address the inherent complexity of cellular systems with massive experimental parallelization and 4D analysis on a single cell level. This review discusses the emerging applications of microfluidic technologies and their advantages for cancer biology and experimental oncolo... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=3971019 Tue, 07 Sep 2010 23:00:00 +0100 3971019 http://www.medworm.com/index.php?rid=3961702&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20829097%26dopt%3DAbstract Authors: Margulies D, Hamilton AD Current approaches to medical diagnostics and drug design are largely based on the ability of monoclonal antibodies or synthetic molecules to bind proteins with high affinity and selectivity. In recent years, however, an alternative approach to protein recognition has emerged, in which proteins are identified using non-specific receptor arrays that are inspired by the olfactory neural system. An ultimate challenge for such systems is realizing a single, high-throughput analytical device that can effectively diagnose a range of medicinally relevant proteins. Such devices might overcome the difficulties associated with designing potent synthetic receptors for proteins and hence, could open up new possibilities in medical diagnostics, pathogen detection, ... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=3961702 Mon, 06 Sep 2010 23:00:00 +0100 3961702 http://www.medworm.com/index.php?rid=3961701&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20829098%26dopt%3DAbstract This article reviews the work performed in the past few years with UCNPs in terms of surface modifications, bioconjugation, and optical (cellular) imaging. PMID: 20829098 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=3961701 Mon, 06 Sep 2010 23:00:00 +0100 3961701 http://www.medworm.com/index.php?rid=3961700&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20829099%26dopt%3DAbstract Authors: Lassila JK The application of computational protein design methods to the design of enzyme active sites offers potential routes to new catalysts and new reaction specificities. Computational design methods have typically treated the protein backbone as a rigid structure for the sake of computational tractability. However, this fixed-backbone approximation introduces its own special challenges for enzyme design and it contrasts with an emerging picture of natural enzymes as dynamic ensembles with multiple conformations and motions throughout a reaction cycle. This review considers the impact of conformational variation and dynamics on computational enzyme design and it highlights new approaches to addressing protein conformational diversity in enzyme design including recent adv... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=3961700 Mon, 06 Sep 2010 23:00:00 +0100 3961700 http://www.medworm.com/index.php?rid=3961704&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20822946%26dopt%3DAbstract Authors: Villali J, Kern D While ground state structures combined with chemical tools and enzyme kinetics deliver useful information on possible chemical mechanisms of enzyme catalysis, they do not unravel the finely balanced energy inventory to explain the impressive rate enhancement of enzymes. For this goal, a complete description of enzyme catalysis in the form of an energy landscape is needed. Since the rate of catalysis is determined by the climb over a sequence of energy barriers, we focus here on the critical question of transition pathways. A combination of time-resolved NMR and simulation deliver a glimpse into how proteins can so efficiently move within the ensemble of the native conformations while avoiding unfolding during that journey. The loss of energy due to breakage o... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=3961704 Thu, 02 Sep 2010 23:00:00 +0100 3961704 http://www.medworm.com/index.php?rid=3961703&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20822947%26dopt%3DAbstract Authors: Ma B, Nussinov R Recent data increasingly reveal that conformational dynamics are indispensable to enzyme function throughout the catalytic cycle, in substrate recruiting, chemical transformation, and product release. Conformational transitions may involve conformational selection and induced fit, which can be viewed as a special case in the catalytic network. NMR, X-ray crystallography, single-molecule FRET, and simulations clearly demonstrate that the free enzyme dynamics already encompass all the conformations necessary for substrate binding, preorganization, transition-state stabilization, and product release. Conformational selection and substate population shift at each step of the catalytic turnover can accommodate enzyme specificity and efficiency. Within such a framew... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=3961703 Thu, 02 Sep 2010 23:00:00 +0100 3961703 http://www.medworm.com/index.php?rid=3961705&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20817542%26dopt%3DAbstract Authors: Anzenbacher P, Liu YL, Kozelkova ME Whether in a glass chip or multi-well plate, differential array sensors are performed as a series of experiments and their output is compared among each other to obtain the differential signals evaluated by pattern recognition methods. To increase the practicality of performing a large number of experiments the sensor elements are often used as semi-wet gels displaying properties of both the solution and the solid state. Due to their semi-wet nature, such array sensors are easier to handle while offering a mechanical support, the affinity of hydrophilic matrices for water aids in analyte transport, and the tunable hydrophilic/hydrophobic nature of the matrices can be used adjusting the preference of the chemosensor membrane for different ana... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=3961705 Wed, 01 Sep 2010 23:00:00 +0100 3961705 http://www.medworm.com/index.php?rid=3933824&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20810304%26dopt%3DAbstract Authors: Williams DH The binding of ligands to proteins can be enhanced through improved packing within the proteins that may, or may not, occur with conformational change. Enzymes can similarly improve their catalytic magic through better packing in the transition state (TS) for reaction. In principle, the improved packing demands no more than the minute shortening of non-covalent interactions throughout much of the structure of the protein (positively cooperative binding). Improved protein packing can account for the remarkably high biotin/streptavidin affinity, and perhaps also for a major part of the catalytic function of hypoxanthine-guanine phosphoribosyltransferase and purine nucleoside phosphorylase (PNP). As successive NAD(+) molecules bind to the glyceraldehyde phosphate dehy... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=3933824 Sun, 29 Aug 2010 23:00:00 +0100 3933824 http://www.medworm.com/index.php?rid=3933825&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20801707%26dopt%3DAbstract In this report, we highlight new 'chemical nose' methodologies that use nanoparticle systems to provide high sensitivity sensing of biomolecular targets, including fluorescent polymer/gold nanoparticle complexes that can discriminate between different bioanalytes including proteins, bacteria, and mammalian cells as well as dye-based micellar systems for the detection of clinically important metalloproteins and nonmetalloproteins. PMID: 20801707 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=3933825 Thu, 26 Aug 2010 23:00:00 +0100 3933825 http://www.medworm.com/index.php?rid=3933826&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20801075%26dopt%3DAbstract Authors: Umali AP, Anslyn EV Differential sensing is continuing to develop as an alternative to traditional, selective chemosensing techniques. This technique takes a cue from how the human senses of taste and smell operate in order to obtain qualitative and even quantitative data on single analytes and mixtures. Whereas classical chemosensing techniques inspired by the 'lock-and-key' approach depend on the development of a selective receptor for a target analyte, pattern-based sensing depends on the development of an array of cross-reactive receptors, which produce a collection of responses upon the array's interaction with a target analyte. This review focuses on an approach to differential sensing that diversifies synthetic receptors to be used in an array via appending combinatoria... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=3933826 Wed, 25 Aug 2010 23:00:00 +0100 3933826 http://www.medworm.com/index.php?rid=3933827&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20800535%26dopt%3DAbstract Authors: Paegel BM Evolution at its heart is an iterative algorithm composed of three steps: selection, amplification and mutagenesis. This algorithm can be applied to complex inputs such as populations of whole organisms and viruses, or mixtures of bare nucleic acids and proteins. The output is the same: evolutionary adaptation of new and improved function subject to selection. Recent breakthroughs in microfluidic technology have introduced automation and process monitoring to in vitro evolution, and reproducible preparation of emulsions and other multi-phase reaction landscapes. It is at this intersection of compartmentalization and in vitro evolution where miniaturization is again redefining experimental design in contemporary chemistry and biology. PMID: 20800535 [PubMed - as s... Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=3933827 Tue, 24 Aug 2010 23:00:00 +0100 3933827 http://www.medworm.com/index.php?rid=3899813&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20729130%26dopt%3DAbstract Authors: Nashine VC, Hammes-Schiffer S, Benkovic SJ Recently, the hypothesis that protein motions are involved in enzymatic turnover has gained significant attention. We review cases where there is evidence that protein motions are rate-limiting in the overall catalytic cycle and examine experimental and theoretical evidence for how such motions enhance the probability of sampling the transition state configurations relative to the ground state. The impact of tunneling, the possible role of vibrational coupling and the value of conformational chemical landscapes are also scrutinized. PMID: 20729130 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=3899813 Thu, 19 Aug 2010 23:00:00 +0100 3899813 http://www.medworm.com/index.php?rid=3899814&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20727817%26dopt%3DAbstract Authors: Stojanovic MN, Worgall TS We will argue for applications of crossreactive arrays of solution-phase sensors in urinalysis, wherein these can be useful for screening, as well as monitoring of disease progress or treatment compliance. For our first demonstration we focus on the detection and classification process of the predominant hydrophobic molecules in urine, steroids, while taking advantage of a variety of differentially crossreactive DNA-based hydrophobic receptors, three-way junctions. We discuss our progress in addressing some of the traditional limitations of crossreactive arrays and what remains to be done to move these systems into clinical applications. PMID: 20727817 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=3899814 Wed, 18 Aug 2010 23:00:00 +0100 3899814 http://www.medworm.com/index.php?rid=3852802&cid=s_35491_60_f&fid=35491&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20692199%26dopt%3DAbstract Authors: Musto CJ, Suslick KS While the complexes between boronic acids and diols have been studied for decades, researchers continue to design new and interesting methods to use these interactions to produce saccharide sensors that are more sensitive and selective. Herein we discuss how the use of pattern-based colorimetric arrays from a collection of crossreactive sensors have been developed as new differential sensing platforms for sugars and related saccharides. PMID: 20692199 [PubMed - as supplied by publisher] (Source: Current Opinion in Chemical Biology) Current Opinion in Chemical Biology journals http://www.medworm.com/rss/comments.php?id=3852802 Wed, 04 Aug 2010 23:00:00 +0100 3852802