Nature Chemical Biology Contents: November 2015, Volume 11 No 11 pp 818 - 887

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TABLE OF CONTENTS November 2015 Volume 11, Issue 11 Commentaries Q&A Research Highlights News and Views Brief Communications Articles Erratum Corrigenda Subscribe   Facebook   RSS   Recommend to library   Twitter   Commentaries Top The ins and outs of selective kinase inhibitor development   pp818 - 821 Susanne Muller, Apirat Chaikuad, Nathanael S Gray and Stefan Knapp doi:10.1038/nchembio.1938 Protein kinases have emerged as one of the most successful families of drug targets. To date, most selective kinase inhibitors have been discovered serendipitously either through broad selectivity screening or through the discovery of unique binding modes. Here we discuss design strategies that could lead to a broader coverage of the kinome with selective inhibitors and to a more rational approach for developing them. Membrane curvature bends the laws of physics and chemistry   pp822 - 825 Lars Iversen, Signe Mathiasen, Jannik Bruun Larsen and Dimitrios Stamou doi:10.1038/nchembio.1941 A 'chemical biology of cellular membranes' must capture the way that mesoscale perturbations tune the biochemical properties of constituent lipid and protein molecules and vice versa. Whereas the classical paradigm focuses on chemical composition, dynamic modulation of the physical shape or curvature of a membrane is emerging as a complementary and synergistic modus operandi for regulating cellular membrane biology. Q&A Top Voices of chemical biology   pp826 - 827 doi:10.1038/nchembio.1951 We asked a collection of chemical biologists: "What advice would you give to a junior scientist interested in pursuing a career in chemical biology?" Research Highlights Top RNA profiling: A better miR trap | Metalloenzymes: A tungsten triple play | Metabolomics: Budgeting on a diet | Glycobiology: Interior decorating | Microbiology: Membranes get the gold | Plant toxicology: Defusing the explosive News and Views Top Ribozymes: How RNA catalyzes cyclization   pp830 - 831 Zhensheng Zhong and Gang Chen doi:10.1038/nchembio.1928 The long-awaited crystal structure of the Varkud satellite (VS) ribozyme dimer provides atomic-level insights into how the VS ribozyme folds and catalyzes RNA circularization during rolling circle replication, as well as revealing convergent evolution used by RNAs to catalyze an SN2 reaction. See also: Article by Suslov et al. Metabolism: Plugging the leak   pp831 - 832 Bryan C Dickinson doi:10.1038/nchembio.1934 Multiple mitochondrial components generate reactive oxygen species (ROS), but separating the consequences of each ROS-generating source from overall mitochondrial health is challenging. A new class of small-molecule inhibitors that selectively block ROS generation from one of the most active sources may provide a new approach toward achieving that goal. See also: Brief Communication by Orr et al. Antibiotics: Synergistic MRSA combinations   pp832 - 833 Karen Bush doi:10.1038/nchembio.1935 Meropenem/piperacillin/tazobactam is a triple β-lactam combination that kills MRSA in vitro and in a mouse model through a novel synergistic mechanism of action. Similar activity for other carbapenem/β-lactam combinations suggests that MRSA infections might be treatable with combinations of established β-lactams currently classified as ineffective against MRSA. See also: Article by Gonzales 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 Brief Communications Top Suppressors of superoxide production from mitochondrial complex III   pp834 - 836 Adam L Orr, Leonardo Vargas, Carolina N Turk, Janine E Baaten, Jason T Matzen et al. doi:10.1038/nchembio.1910 High-throughput chemical screening identified several groups of compounds that selectively block superoxide production from the outer Q-binding site of mitochondrial complex III and protect against ROS-induced oxidative stress in pancreatic β cells. Chemical compounds See also: News and Views by Dickinson Two cytochromes P450 catalyze S-heterocyclizations in cabbage phytoalexin biosynthesis   pp837 - 839 Andrew P Klein and Elizabeth S Sattely doi:10.1038/nchembio.1914 The identification and characterization of two cytochromes P450 from cabbage establish the biochemical basis for synthesizing brassinin-based phytoalexins, using two different routes of S-heterocyclization to construct these important vegetable compounds. Articles Top Crystal structure of the Varkud satellite ribozyme   pp840 - 846 Nikolai B Suslov, Saurja DasGupta, Hao Huang, James R Fuller, David M J Lilley et al. doi:10.1038/nchembio.1929 Crystal structures of the full-length VS ribozyme show a domain-swapped dimer that reveals potential mechanisms for cis and trans processing, and suggest convergent evolution in the active site motifs across multiple ribozymes. See also: News and Views by Zhong & Chen Notch-modifying xylosyltransferase structures support an SNi-like retaining mechanism   pp847 - 854 Hongjun Yu, Megumi Takeuchi, Jamie LeBarron, Joshua Kantharia, Erwin London et al. doi:10.1038/nchembio.1927 Structural and biochemical investigations of a xylosyltransferase in complex with a domain from its substrate Notch inform on the catalytic mechanism and the conformational rearrangements needed for substrate binding, while genetic analysis poses new questions in cancer biology. Synergistic, collaterally sensitive β-lactam combinations suppress resistance in MRSA   pp855 - 861 Patrick R Gonzales, Mitchell W Pesesky, Renee Bouley, Anna Ballard, Brent A Biddy et al. doi:10.1038/nchembio.1911 Triple combinations of carbapenem, penicillin and β-lactamase inhibitor antibiotic classes are synergistic against MRSA through a mechanism involving allostery-based synergy and collateral sensitivity and can thus be applied at doses that lead to less resistance. See also: News and Views by Bush Determinants of amyloid fibril degradation by the PDZ protease HTRA1   pp862 - 869 Simon Poepsel, Andreas Sprengel, Barbara Sacca, Farnusch Kaschani, Markus Kaiser et al. doi:10.1038/nchembio.1931 The serine protease HTRA1 utilizes a "disintegration" mechanism involving its flexible PDZ domains to first loosen tau amyloid fibrils and subsequently disintegrating the fibrillar core structure for efficient proteolytic degradation. Translocation-coupled DNA cleavage by the Type ISP restriction-modification enzymes   pp870 - 877 Mahesh K Chand, Neha Nirwan, Fiona M Diffin, Kara van Aelst, Manasi Kulkarni et al. doi:10.1038/nchembio.1926 Crystal structure of the Type ISP restriction enzyme-DNA complex and single-molecule studies reveal that DNA cleavage occurs through remodeling of ATPase-DNA interactions resulting in translocation of the enzyme without loop formation. New IDH1 mutant inhibitors for treatment of acute myeloid leukemia   pp878 - 886 Ujunwa C Okoye-Okafor, Boris Bartholdy, Jessy Cartier, Enoch N Gao, Beth Pietrak et al. doi:10.1038/nchembio.1930 Gain of function mutations in isocitrate dehydrogenase 1 (IDH1) have been detected in cases of acute myeloid leukemia (AML). The application of an allosteric IDH1 inhibitor in AML cells promotes blast differentiation and restores DNA cytosine methylation patterns. Chemical compounds Corrigenda Top Corrigendum: Protein degradation: Prime time for PROTACs   p887 Raymond J Deshaies doi:10.1038/nchembio1115-887b Corrigendum: The promise and peril of chemical probes   p887 Cheryl H Arrowsmith, James E Audia, Christopher Austin, Jonathan Baell, Jonathan Bennett et al. doi:10.1038/nchembio1115-887c Erratum Top Erratum: Reinvigorating natural product combinatorial biosynthesis with synthetic biology   p887 Eunji Kim, Bradley S Moore and Yeo Joon Yoon doi:10.1038/nchembio1115-887a Top Advertisement Nature Microbiology: Call for Papers Launching in January 2016, Nature Microbiology is now open for submissions and inviting high-quality submissions. 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