Nature Chemical Biology Contents: December 2015, Volume 11 No 12 pp 889 - 993

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TABLE OF CONTENTS December 2015 Volume 11, Issue 12 Editorial Commentaries Q&A Research Highlights News and Views Perspectives Reviews Brief Communications Articles Subscribe   Facebook   RSS   Recommend to library   Twitter   Focus Top Focus on Frontiers in chemical biology This special issue, the last of our 10th anniversary volume, presents a collection of articles focused on "Frontiers in chemical biology" and identifies some of the emerging scientific areas that will engage chemical biologists in the coming years. Focus on Frontiers in chemical biology Editorial Top Future perfect   p889 doi:10.1038/nchembio.1977 Abundant frontiers at the interface of chemistry and biology promise another decade of technological innovation and scientific discovery by chemical biologists. Commentaries Top Targeting transcription is no longer a quixotic quest   pp891 - 894 Anna K Mapp, Rachel Pricer and Steven Sturlis doi:10.1038/nchembio.1962 Misregulated transcription factors play prominent roles in human disease, but their dynamic protein-protein interaction network has long made the goal of transcription-targeted therapeutics impractical. Recent advances in technologies for modulating protein interaction networks mean that the end of the quest is in sight. XFELs open a new era in structural chemical biology   pp895 - 899 Petra Fromme doi:10.1038/nchembio.1968 X-ray crystallography, the workhorse of structural biology, has been revolutionized by the advent of serial femtosecond crystallography using X-ray free electron lasers. Here, the fast pace and history of discoveries are discussed together with current challenges and the method's great potential to make new structural discoveries, such as the ability to generate molecular movies of biomolecules at work. Q&A Top Voices of chemical biology   pp900 - 901 doi:10.1038/nchembio.1975 We asked a collection of chemical biologists: "What is the most exciting frontier area in chemical biology, and what key technology is needed to advance knowledge and applications at this frontier?" Research Highlights Top Tumor immunology: Assembling the T cell | Intrinsically disordered proteins: I like to move it, move it | Metabolism: Some assembly required | RNA modification: Stressing the message | Metals: A hydride out of hiding | Riboswitches: A bacterial antivitamin News and Views Top Chemical libraries: How dark is HTS dark matter?   pp904 - 905 Ricardo Macarron doi:10.1038/nchembio.1937 Selecting compounds for the chemical library is the foundation of high-throughput screening (HTS). After some years and multiple HTS campaigns, many molecules in the Novartis and NIH Molecular Libraries Program screening collections have never been found to be active. An in-depth exploration of the bioactivity of this 'dark matter' does in fact reveal some compounds of interest. See also: Article by Wassermann et al. Virology: MicroRNA-lipid one-upmanship   pp905 - 906 Patricia A Thibault and Joyce A Wilson doi:10.1038/nchembio.1953 25-Hydroxycholesterol induces miR-185 to suppress lipid and cholesterol synthesis pathways and inhibit viruses such as hepatitis C virus (HCV), that use host membranes to propagate. HCV counteracts this by suppressing miR-185 expression to drive increased cellular lipid content. See also: Article by Singaravelu et al. RNA folding: A clear path to RNA catalysis   pp906 - 908 Amanda Solem and Alain Laederach doi:10.1038/nchembio.1954 A new high-resolution crystal structure of the subdomain from a catalytically active group II intron reveals important conformational rearrangements necessary to achieve the fully formed catalyst. This structure provides the first atomic-resolution structure of an RNA folding intermediate. See also: Article by Zhao et al. Chemical Biology JOBS of the week Faculty Position in Chemistry / Chemical Biology Cornell University Postdoctoral Position - Chemical Biology St. Jude Children's Research Hospital (SJCRH) Postdoctoral fellow position in iPSC research Icahn School of Medicine at Mount Sinai 2016 Postdoctoral Fellowship Program Monterey Bay Aquarium Research Institute (MBARI) Postdoctoral Research Assistant (1 FTE) University of Dundee More Science jobs from Chemical Biology EVENT State of the Brain 22 - 26 May 2016 Alpbach, Austria More science events from Perspectives Top Discovery and characterization of smORF-encoded bioactive polypeptides   pp909 - 916 Alan Saghatelian and Juan Pablo Couso doi:10.1038/nchembio.1964 Imaging and manipulating proteins in live cells through covalent labeling   pp917 - 923 Lin Xue, Iuliia A Karpenko, Julien Hiblot and Kai Johnsson doi:10.1038/nchembio.1959 Chemical modulators of ribosome biogenesis as biological probes   pp924 - 932 Jonathan M Stokes and Eric D Brown doi:10.1038/nchembio.1957 Reviews Top Progress and challenges for chemical probing of RNA structure inside living cells   pp933 - 941 Miles Kubota, Catherine Tran and Robert C Spitale doi:10.1038/nchembio.1958 Functional genomics to uncover drug mechanism of action   pp942 - 948 Sebastian M B Nijman doi:10.1038/nchembio.1963 Brief Communications Top Polyketide synthase chimeras reveal key role of ketosynthase domain in chain branching   pp949 - 951 Srividhya Sundaram, Daniel Heine and Christian Hertweck doi:10.1038/nchembio.1932 Some polyketide synthase pathways include branching modules that insert branched monomers into polyketide products. In vitro reconstitution using swapped domains now shows that the mysterious branching (B) domain and the homologous X domain in these modules have structural rather than catalytic roles. Light-assisted small-molecule screening against protein kinases   pp952 - 954 Alvaro Ingles-Prieto, Eva Reichhart, Markus K Muellner, Matthias Nowak, Sebastian M B Nijman et al. doi:10.1038/nchembio.1933 The combination of a light-activated receptor tyrosine kinase and a fluorescent MAPK/ERK reporter results in the development of an optogenetics-based cell screening method to identify small-molecule inhibitors of RTK signaling. Functional and structural characterization of a heparanase   pp955 - 957 Lisa Bohlmann, Gregory D Tredwell, Xing Yu, Chih-Wei Chang, Thomas Haselhorst et al. doi:10.1038/nchembio.1956 Structure and functional characterization of BpHep, a heparanase from the invasive pathogenic bacterium Burkholderia pseudomallei, defines its glycosaminoglycan recognition mechanism and its catalytic mechanism as an endo-acting glycoside hydrolase. Chemical compounds Articles Top Dark chemical matter as a promising starting point for drug lead discovery   pp958 - 966 Anne Mai Wassermann, Eugen Lounkine, Dominic Hoepfner, Gaelle Le Goff, Frederick J King et al. doi:10.1038/nchembio.1936 Unique activities and high potency at disease-relevant biological targets can now be identified for /`dark chemical matter/'—compounds in high-throughput screening libraries that have been extensively tested but that have never been annotated as having biological activity. See also: News and Views by Macarron Crystal structure of group II intron domain 1 reveals a template for RNA assembly   pp967 - 972 Chen Zhao, Kanagalaghatta R Rajashankar, Marco Marcia and Anna Marie Pyle doi:10.1038/nchembio.1949 A crystal structure of an RNA folding intermediate of the group II intron reveals a compact conformation that is stabilized by the sequential docking of downstream intron domains, providing new insights into RNA tertiary structure assembly. See also: News and Views by Solem & Laederach A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease   pp973 - 980 Trevor Dale, Paul A Clarke, Christina Esdar, Dennis Waalboer, Olajumoke Adeniji-Popoola et al. doi:10.1038/nchembio.1952 Chemoproteomic studies have revealed that a Wnt-pathway inhibitor, CCT251545, is a potent and selective small-molecule chemical probe that inhibits the Mediator complex-associated protein kinases CDK8 and CDK19 through a type 1 binding mode and modulates the growth of Wnt-dependent tumors. Chemical compounds Mapping the energy landscape for second-stage folding of a single membrane protein   pp981 - 987 Duyoung Min, Robert E Jefferson, James U Bowie and Tae-Young Yoon doi:10.1038/nchembio.1939 Single-molecule experiments reveal the unfolding and refolding landscape of the rhomboid protease GlpG in a native-like lipid membrane. GlpG unravels cooperatively in a single step and has a large unfolding barrier, making for a long-lived folded state. MicroRNAs regulate the immunometabolic response to viral infection in the liver   pp988 - 993 Ragunath Singaravelu, Shifawn O'Hara, Daniel M Jones, Ran Chen, Nathan G Taylor et al. doi:10.1038/nchembio.1940 25-Hydroxycholesterol induces expression of the microRNAs miR-130b and miR-185 in HCV-infected cells, and these inhibit viral fatty acid desaturation, lipid uptake and biosynthesis, thereby limiting infection. HCV counteracts this immunometabolic response by downregulating these microRNAs. See also: News and Views by Thibault & Wilson 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. 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