Nature Chemical Biology Contents: January 2013 Volume 9 Number 1, pp 1 - 64

TABLE OF CONTENTS January 2013 Volume 9, Issue 1 Editorial Commentary Research Highlights News and Views Brief Communications Articles Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement nature.com webcasts Macmillan Science Communication, Exclusive partner of Nature Publishing Group, Publisher of Nature and Scientific American presented a custom webcast in January 2013 on: Using Flow Cytometry in Drinking Water Microbiology Register and watch the webcast online Free online www.nature.com/webcasts Sponsored by: BD Biosciences   Editorial Top Risky business   p1 doi:10.1038/nchembio.1155 Public-private partnerships can reinvigorate precompetitive scientific research and de-risk drug discovery programs to help them meet demand for better and safer therapies. Commentary Top A public-private partnership to unlock the untargeted kinome   pp3 - 6 Stefan Knapp, Paulo Arruda, Julian Blagg, Stephen Burley, David H Drewry, Aled Edwards, Doriano Fabbro, Paul Gillespie, Nathanael S Gray, Bernhard Kuster, Karen E Lackey, Paulo Mazzafera, Nicholas C O Tomkinson, Timothy M Willson, Paul Workman and William J Zuercher doi:10.1038/nchembio.1113 Chemical probes are urgently needed to functionally annotate hitherto-untargeted kinases and stimulate new drug discovery efforts to address unmet medical needs. The size of the human kinome combined with the high cost associated with probe generation severely limits access to new probes. We propose a large-scale public-private partnership as a new approach that offers economies of scale, minimized redundancy and sharing of risk and cost. Research Highlights Top Structural biology: E2 loader | Glycobiology: Telling twins apart | Cancer: Feeding forward and back | Nuclear transport: Bicycle built for two | Neuroscience: A long wait to refuel | Signaling: Selecting the second messenger | Membranes: PTEN heeds the charge | Metabolism: A model merger News and Views Top Protein engineering: Making ubiquitin specific   pp10 - 11 Titia K. Sixma doi:10.1038/nchembio.1143 Conformational targeting enabled the creation of a ubiquitin variant that specifically inhibits the deubiquitinating enzyme ubiquitin-specific protease 7 (also known as HAUSP). Generation of such tools is essential to unravel the complexities of ubiquitin signaling, but how general is this approach? See also: Article by Zhang et al. Enzymes: Nailing down hydrogenase   pp11 - 12 Michael J. Maroney doi:10.1038/nchembio.1139 Aerobic inactivation of hydrogenases is a serious limitation to applications of the enzyme in biotechnology and has been extensively studied. A recent investigation combining electrochemical and spectroscopic methods shows that the molecular species that form as a result of exposure to O2 can be formed anaerobically and thus cannot involve incorporation of oxygen in the enzyme. See also: Brief Communication by Abou Hamdan et al. Protein folding: Salty sea regulators of cystic fibrosis   pp12 - 14 Vijay Gupta and William E Balch doi:10.1038/nchembio.1144 New, bioactive marine sponge compounds that function as inhibitors of the poly (ADP-ribose) polymerase family of proteins have now been identified to promote the correction of cystic fibrosis. Poly (ADP-ribose) polymerase inhibitors may be managers of proteostasis biology, consistent with their role (or roles) in remediation of inflammatory states. Chemical Biology JOBS of the week 4-year PhD Interdisciplinary Programme in Structural, Computational and Chemical Biology at UCL / Birkbeck / NIMR ISMB (Birkbeck/UCL) Tenure-Track Assistant Professor in Analytical Chemistry / Chemical Biology (2 Posts) University of Hong Kong Assistant Professor in Chemical Engineering McGill University Postdoctoral fellowship in chemical biology Mount Sinai School of Medicine More Science jobs from Chemical Biology EVENT 4th International Conference for Young Chemists (ICYC) 30 January-1 February, 2013 Penang, Malaysia More science events from Brief Communications Top O2-independent formation of the inactive states of NiFe hydrogenase   pp15 - 17 Abbas Abou Hamdan, Bénédicte Burlat, Oscar Gutiérrez-Sanz, Pierre-Pol Liebgott, Carole Baffert, Antonio L De Lacey, Marc Rousset, Bruno Guigliarelli, Christophe Léger and Sébastien Dementin doi:10.1038/nchembio.1110 Biotechnological applications of hydrogenases are limited by their susceptibility to inactivation by oxygen, thought to proceed by trapping a reduced O2 in the active site. Electrochemical and spectroscopic studies using various electron acceptors now show that oxygen inactivation is not linked to oxygen atom donation. See also: News and Views by Maroney RNA SHAPE analysis in living cells   pp18 - 20 Robert C Spitale, Pete Crisalli, Ryan A Flynn, Eduardo A Torre, Eric T Kool and Howard Y Chang doi:10.1038/nchembio.1131 Selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE) is a proven methodology for in vitro RNA secondary structure analysis. The identification of a new acylating agent permits the use of SHAPE to probe folded RNAs within living cells. Chemical compounds Articles Top Biomimetic diversity-oriented synthesis of benzannulated medium rings via ring expansion   pp21 - 29 Renato A Bauer, Todd A Wenderski and Derek S Tan doi:10.1038/nchembio.1130 Medium-sized ring structures can provide unique entry points into natural product–like chemical space but are synthetically challenging to access. A biologically inspired method eases these challenges, employing a dearomatization-rearomatization sequence to form a diverse library of rings from tailored bicyclic compounds. Chemical compounds Identification of DES1 as a vitamin A isomerase in Müller glial cells of the retina   pp30 - 36 Joanna J Kaylor, Quan Yuan, Jeremy Cook, Shanta Sarfare, Jacob Makshanoff, Anh Miu, Anita Kim, Paul Kim, Samer Habib, C Nathaniel Roybal, Tongzhou Xu, Steven Nusinowitz and Gabriel H Travis doi:10.1038/nchembio.1114 Equilibrium isomerization of retinol is a new activity now attributable to DES1. 11-cis-retinol synthesized by DES1 in Müller cells of the retina can be converted to the visual chromophore for regenerating opsin pigment in cone photoreceptors. Structure and function of a unique pore-forming protein from a pathogenic acanthamoeba   pp37 - 42 Matthias Michalek, Frank D Sönnichsen, Rainer Wechselberger, Andrew J Dingley, Chien-Wen Hung, Annika Kopp, Hans Wienk, Maren Simanski, Rosa Herbst, Inken Lorenzen, Francine Marciano-Cabral, Christoph Gelhaus, Thomas Gutsmann, Andreas Tholey, Joachim Grötzinger and Matthias Leippe doi:10.1038/nchembio.1116 Acanthaporin is identified as a pore-forming protein from the infectious Acanthamoeba culbertsoni with a previously unknown structure. The newly identified structure includes a pH-dependent histidine switch that controls partitioning between the inactive dimer and the active monomer, which assembles into larger species to cause toxicity. Active site profiling reveals coupling between domains in SRC-family kinases   pp43 - 50 Ratika Krishnamurty, Jennifer L Brigham, Stephen E Leonard, Pratistha Ranjitkar, Eric T Larson, Edward J Dale, Ethan A Merritt and Dustin J Maly doi:10.1038/nchembio.1118 Src family kinase mutants, with altered regulatory domain interactions, were profiled with a photodependent crosslinking strategy to reveal conformation-specific ATP-competitive inhibitors that affect intermolecular binding interactions. Chemical compounds Conformational stabilization of ubiquitin yields potent and selective inhibitors of USP7    pp51 - 58 Yingnan Zhang, Lijuan Zhou, Lionel Rouge, Aaron H Phillips, Cynthia Lam, Peter Liu, Wendy Sandoval, Elizabeth Helgason, Jeremy M Murray, Ingrid E Wertz and Jacob E Corn doi:10.1038/nchembio.1134 Stabilization of ubiquitin's β1-β2 region by computational design and phage display, targeting both buried and surface residues, yields a ubiquitin variant that specifically inhibits the deubiquitinase USP7 in vitro and in cells. See also: News and Views by Sixma Peptidomic discovery of short open reading frame–encoded peptides in human cells   pp59 - 64 Sarah A Slavoff, Andrew J Mitchell, Adam G Schwaid, Moran N Cabili, Jiao Ma, Joshua Z Levin, Amir D Karger, Bogdan A Budnik, John L Rinn and Alan Saghatelian doi:10.1038/nchembio.1120 The human genome contains stretches of DNA sequence with unknown function. Peptidomics coupled to RNA-Seq now reveals a class of short open reading frames in human genomes that are translated into small peptides. Top Advertisement Subscribe today to Nature Chemical Biology Reflecting the diversity and excitement of chemical biology research. Subscribe online here today: https://secure.nature.com/subscribe/nchembio   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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