Nature Chemical Biology Contents: June 2015, Volume 11 No 6 pp 363 - 437

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TABLE OF CONTENTS June 2015 Volume 11, Issue 6 Focus Editorial Special Feature Commentaries Q&A Research Highlights News and Views Perspective Brief Communication Articles Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Communications is now fully open access All new submissions if accepted, will be published open access and an article processing charge will apply. For more information visit the website. Visit our open access funding page or contact openaccess@nature.com to learn more on APC funding.     Advertisement New to NPG from Apr 2015 Co-published by Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) and Nature Publishing Group, Sister Journal to Cell Research. Cell Discovery is a new online open access, fully peer-reviewed journal publishes results of significance and originality in all areas of molecular & cell biology.  Discover more about Cell Discovery     Focus Top 10th Anniversary With the June 2015 issue, Nature Chemical Biology celebrates 10 years of serving the chemical biology community. In honor of this anniversary, we are presenting a collection of articles that highlights the scientific accomplishments and promising future of chemical biology. 10th Anniversary Editorial Top What's in a name?   p363 doi:10.1038/nchembio.1832 Chemical biology may elude simple definitions, but there remains no question that chemical biologists have crafted a compelling interdisciplinary narrative that advances science and benefits society. Special Feature Top Greatest hits   pp364 - 367 doi:10.1038/nchembio.1815 We present a selection of papers published in Nature Chemical Biology over the past decade that reflect the diversity and excitement of chemical biology research. Commentaries Top Know your target, know your molecule   pp368 - 372 Mark E Bunnage, Adam M Gilbert, Lyn H Jones and Erik C Hett doi:10.1038/nchembio.1813 The pharmaceutical industry continues to experience significant attrition of drug candidates during phase 2 proof-of-concept clinical studies. We describe some questions about the characteristics of protein targets and small-molecule drugs that may be important to consider in drug-discovery projects and could improve prospects for future clinical success. Layers of structure and function in protein aggregation   pp373 - 377 Motomasa Tanaka and Yusuke Komi doi:10.1038/nchembio.1818 Protein aggregation is a central hallmark of many neurodegenerative disorders, but the relationship of aggregate structural diversity to the resultant cellular cytotoxicity and phenotypic diversity has remained obscure. Recent advances in understanding the mechanisms of protein aggregation and their physiological consequences have been achieved through chemical biology approaches, such as rationally designed protein modifications and chemical probes, providing crucial mechanistic insights and promise for therapeutic strategies for brain disorders. Q&A Top Voices of chemical biology   pp378 - 379 doi:10.1038/nchembio.1820 Agreeing on a precise definition of chemical biology has been a persistent challenge for the field. We asked a diverse group of scientists to "define chemical biology" and present a selection of responses. Research Highlights Top Proteostasis: Found in translation | Archaeochemistry: Raising a glass | Protein structure/folding: Shape your duty | Brain cancer: Staying alive | Carbohydrates: Inhibitors in an instant | Cell motility: Bigger and faster News and Views Top Pharmacodynamics: Which trails are your drugs taking?   pp382 - 383 Rumin Zhang doi:10.1038/nchembio.1795 Binding kinetics (BK) has an indispensable role in pharmacodynamics (PD). Incorporating slow BK into a mechanistic PD model is shown to have predictive value for in vitro cellular and in vivo animal antibacterial efficacy. Membrane fusion: A new role for lipid domains?   pp383 - 384 Erwin London doi:10.1038/nchembio.1812 Boundaries between ordered and disordered membrane domains may be the site of HIV fusion protein insertion into its target membrane. Enzyme pathways: C1 metabolism redesigned   pp384 - 386 Yi-Shu Tai and Kechun Zhang doi:10.1038/nchembio.1819 One-carbon metabolic pathways create new opportunities for metabolic engineering, but natural pathways have limitations in catalytic efficiency and interspecies transferability. Now a computationally designed enzyme, formolase, enables the construction of a synthetic metabolic pathway in Escherichia coli for assimilation of formate into a glycolytic intermediate in only five reaction steps. Chemical Biology JOBS of the week Center for Cell Ultrastructure & Morphology, Director The Scripps Research Institute (TSRI) Postdoctoral Research Assistant University of Oxford Research Laboratory Head / Drug Discovery in Cancer Immunotherapy (m / f) Boehringer Ingelheim Senior Fellow - Parkinson's Disease Research University of Washington Senior Scientist - Tenure Track Paul Scherrer Institut (PSI) More Science jobs from Chemical Biology EVENT The Expanding Toolbox of Medicinal Chemistry: From Chemical Biology to Clinical Applications 16 October 2015 Dijon, France More science events from Perspective Top Application guide for omics approaches to cell signaling   pp387 - 397 Zhong Yao, Julia Petschnigg, Robin Ketteler and Igor Stagljar doi:10.1038/nchembio.1809 This perspective discusses recent advances in high-throughput omics approaches such as proteomic and interactome profiling and genetic perturbations that allow the identification and alterations of cell signaling networks. Brief Communication Top The use of ene adducts to study and engineer enoyl-thioester reductases   pp398 - 400 Raoul G Rosenthal, Bastian Vogeli, Nick Quade, Guido Capitani, Patrick Kiefer et al. doi:10.1038/nchembio.1794 The use of a presumed chemical intermediate in the mechanism of enoyl thioester reductase enables the identification of the long-sought proton donor and the rational redesign of enzyme stereoselectivity. Chemical compounds Articles Top Mode of action and pharmacogenomic biomarkers for exceptional responders to didemnin B   pp401 - 408 Malia B Potts, Elizabeth A McMillan, Tracy I Rosales, Hyun Seok Kim, Yi-Hung Ou et al. doi:10.1038/nchembio.1797 The natural product didemnin B inhibits PPT1 and the antiapoptotic protein Mcl-1 in particular types of cancer cells containing a unique genetic profile that correlates with drug sensitivity. Catalytic mechanism of a retinoid isomerase essential for vertebrate vision   pp409 - 415 Philip D Kiser, Jianye Zhang, Mohsen Badiee, Qingjiang Li, Wuxian Shi et al. doi:10.1038/nchembio.1799 Retinoid isomerase is a critical enzyme in the conversion of retinyl esters to 11-cis-retinol, a key step in the regeneration of visual pigments that mediate light perception. Structural, biochemical and modeling data using substrate analogs explain how this unusual reaction proceeds. Chemical compounds Translating slow-binding inhibition kinetics into cellular and in vivo effects   pp416 - 423 Grant K Walkup, Zhiping You, Philip L Ross, Eleanor K H Allen, Fereidoon Daryaee et al. doi:10.1038/nchembio.1796 Drug-target residence time is viewed as a predictor of the clinical efficacy of small-molecule drugs. A pharmacodynamic model, taking into account the target binding kinetics of antibacterial compounds, leads to accurate predictions of cellular and in vivo efficacies of the inhibitors. Chemical compounds HIV gp41-mediated membrane fusion occurs at edges of cholesterol-rich lipid domains   pp424 - 431 Sung-Tae Yang, Volker Kiessling, James A Simmons, Judith M White and Lukas K Tamm doi:10.1038/nchembio.1800 Fusion of HIV with target membranes via the HIV fusion peptide requires phase separation among lipids as well as phase heterogeneity because the fusion is biased toward the boundary between regions of ordered (so-called rafts) and disordered lipids. A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models   pp432 - 437 Elayne Chan-Penebre, Kristy G Kuplast, Christina R Majer, P Ann Boriack-Sjodin, Tim J Wigle et al. doi:10.1038/nchembio.1810 Protein methyltransferase PRMT5 symmetrically dimethylates arginine residues in proteins, including histones, and has been associated with tumorigenesis. The identification of EPZ015666 as a potent chemical probe of PRMT5 could promote understanding of the role of PRMT5 in human disease both in cells and in vivo. Chemical compounds Top Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. Find the latest scientific conferences, courses, meetings and symposia on natureevents.com. For event advertising opportunities across the Nature Publishing Group portfolio please contact natureevents@nature.com More Nature Events

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