Nature Chemical Biology Contents: October 2014 Volume 10 No 10 pp 794 - 867

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TABLE OF CONTENTS October 2014 Volume 10, Issue 10 Research Highlights News and Views Review Brief Communications Articles Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement nature.com webcasts Macmillan Science Communication presents a custom webcast on: An integrated OMICs approach to cancer progression Thursday October 23, 8am PDT, 11am EDT, 4pm BST, 5pm CEST  Register for the webcast and live Q and A session Sponsored by:       Research Highlights Top ER stress: Redox trade-off | DNA demethylation: lncRNA express delivery | Nanowires: String me along | Lipids: Flexible fill-ins | Carbohydrates: Xylan feels the pinch | Biosynthesis: All together now | Pharmacological chaperones: α-Helical masquerade | Transporters: Death by ions News and Views Top Kinase inhibitors: An allosteric add-on   pp796 - 797 Zachariah H Foda and Markus A Seeliger doi:10.1038/nchembio.1630 Development of highly specific kinase inhibitors has been a long-standing challenge in chemical biology. The structural and mechanistic characterization of an Erk1/2 kinase inhibitor provides new strategies to develop specific kinase inhibitors by targeting a binding pocket adjacent to the ATP binding site. See also: Article by Chaikuad et al. Small-molecule inhibitors: Viral fusion arrested   pp797 - 798 Andrew B Ward doi:10.1038/nchembio.1632 A newly discovered small molecule with broad reactivity against diverse HIV-1 strains prevents the surface envelope glycoprotein from fusing with host cells and offers a potential new anti-HIV-1 target. See also: Article by Herschhorn et al. Biosynthesis: Bioinformatics bolster a renaissance   pp798 - 800 Segolene Caboche doi:10.1038/nchembio.1634 Biosynthetic gene clusters encode the enzymatic pathways to make secondary metabolites, molecules of great interest for the pharmaceutical and biotechnology industries. Access to an increasing number of microbial genomes, coupled with efficient bioinformatic tools, is creating new momentum in secondary metabolite research. Chemical Biology JOBS of the week Postdoctoral Research Associate in Chemical Biology Arizona State University Tenure-Track Faculty Positions in Chemical Biology University of Utah Assistant / Associate / Full Professor in Chemical Biology, University of California, Davis University of California - Davis Lecturer in Bio-Organic Chemistry University of East Anglia (UEA) Faculty Positions Memorial Sloan Kettering Cancer Center (MSKCC) More Science jobs from Chemical Biology EVENT RSC: Translational Biocatalysis 16 December 2014 London, UK More science events from Review Top Photochemistry of flavoprotein light sensors   pp801 - 809 Karen S Conrad, Craig C Manahan and Brian R Crane doi:10.1038/nchembio.1633 Exposure to blue light promotes changes in the protein conformation of flavin photosensors. A review of recent advances in these light sensors discusses key questions in the field and their application to engineer light-mediated molecular switches. Brief Communications Top Archaeal Elp3 catalyzes tRNA wobble uridine modification at C5 via a radical mechanism   pp810 - 812 Kiruthika Selvadurai, Pei Wang, Joseph Seimetz and Raven H Huang doi:10.1038/nchembio.1610 The eukaryotic Elongator complex has been assigned multiple roles in transcription and tRNA modification. In archaea, the Elp3 component is a radical SAM enzyme that catalyzes the carboxymethylation of uridine in the wobble position of tRNA. An allosteric modulator to control endogenous G protein-coupled receptors with light   pp813 - 815 Silvia Pittolo, Xavier Gómez-Santacana, Kay Eckelt, Xavier Rovira, James Dalton et al. doi:10.1038/nchembio.1612 Alloswitch-1 is a photoswitchable modulator for mGlu5, and it is the first photoswitchable allosteric GPCR modulator. It was generated by adding the azobenzene Ar-N=N-Ar scaffold into an existing positive allosteric modulator of the receptor. Chemical compounds Articles Top Engineered oligosaccharyltransferases with greatly relaxed acceptor-site specificity   pp816 - 822 Anne A Ollis, Sheng Zhang, Adam C Fisher and Matthew P DeLisa doi:10.1038/nchembio.1609 Production of eukaryotic proteins in bacteria is limited by the specificity of the bacterial oligosaccharyltransferases that perform N-linked glycosylation. ‘GlycoSNAP’ simplifies the study of these enzymes, leading to mutants with relaxed specificity. Discovery of a new ATP-binding motif involved in peptidic azoline biosynthesis   pp823 - 829 Kyle L Dunbar, Jonathan R Chekan, Courtney L Cox, Brandon J Burkhart, Satish K Nair et al. doi:10.1038/nchembio.1608 A two-enzyme complex works as a cyclodehydratase to form TOMM natural products, but the roles of each protein have been unclear. Structural and biochemical analysis deconvolutes the roles of each protein and identifies a new ATP-binding motif. A chemical inhibitor of jasmonate signaling targets JAR1 in Arabidopsis thaliana   pp830 - 836 Christian Meesters, Timon Mönig, Julian Oeljeklaus, Daniel Krahn, Corey S Westfall et al. doi:10.1038/nchembio.1591 Jasmonate derivatives regulate numerous defense and developmental pathways in plants. A chemical screen in Arabidopsis thaliana identifies jarin-1 as an inhibitor of jasmonate biosynthesis and a potential chemical probe of jasmonate signaling. Chemical compounds A microbial biomanufacturing platform for natural and semisynthetic opioids   pp837 - 844 Kate Thodey, Stephanie Galanie and Christina D Smolke doi:10.1038/nchembio.1613 Metabolic engineering of yeast to incorporate plant and bacterial enzymes that construct and decorate morphine, along with spatial engineering to enable a spontaneous chemical reaction, provides strains capable of producing up to 130 mg/l of opioids. A broad HIV-1 inhibitor blocks envelope glycoprotein transitions critical for entry   pp845 - 852 Alon Herschhorn, Christopher Gu, Nicole Espy, Jonathan Richard, Andrés Finzi et al. doi:10.1038/nchembio.1623 HIV-1 binds host CD4+ T cells via its gp120 envelope glycoprotein that undergoes changes to allow ‘opening’ of the envelope trimer, exposure of gp41 and binding to the CCR5 co-receptor. Compound 18A inhibits HIV-1 infection by blocking some of these conformational changes. Chemical compounds See also: News and Views by Ward A unique inhibitor binding site in ERK1/2 is associated with slow binding kinetics   pp853 - 860 Apirat Chaikuad, Eliana M C Tacconi, Jutta Zimmer, Yanke Liang, Nathanael S Gray et al. doi:10.1038/nchembio.1629 Crystallographic analysis depicting the interaction of the kinase inhibitor SCH772984 with ERK1/2 reveals a unique binding pocket distinct from off-targets such as haspin and is associated with slow binding kinetics and prolonged inhibitory activity. Chemical compounds See also: News and Views by Foda & Seeliger Solid-to-fluid DNA transition inside HSV-1 capsid close to the temperature of infection   pp861 - 867 Udom Sae-Ueng, Dong Li, Xiaobing Zuo, Jamie B Huffman, Fred L Homa et al. doi:10.1038/nchembio.1628 Single-molecule measurements show that HSV-1 DNA changes its stiffness by undergoing a solid-to-fluid transition within the capsid in the ionic environment of host cells and at a temperature that is optimal for viral infection. Top Advertisement Scientific Reports is now accepting submissions from all scientific fields including clinical sciences. Online and open access, Scientific Reports is a primary research publication from the publishers of Nature, covering all areas of the natural and clinical sciences. 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