Nature Chemical Biology Contents: July 2015, Volume 11 No 7 pp 438 - 532

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TABLE OF CONTENTS July 2015 Volume 11, Issue 7 Commentaries Q&A Research Highlights News and Views Perspective Articles Errata 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.   Commentaries Top Quo vadis, enzymology?   pp438 - 441 Chaitan Khosla doi:10.1038/nchembio.1844 Enzymology has been a vital link between chemistry and biology in the second half of the twentieth century. A range of emerging scientific challenges is presenting the field with exciting opportunities to continue thriving in the future. Iron-sulfur proteins hiding in plain sight   pp442 - 445 Tracey A Rouault doi:10.1038/nchembio.1843 Recent studies suggest that iron-sulfur (Fe-S) proteins may be unexpectedly abundant and functionally diverse in mammalian cells, but their identification still remains difficult. The use of informatics along with traditional spectroscopic analyses could be key to discovering new Fe-S proteins and validating their functional roles. Q&A Top Voices of chemical biology   pp446 - 447 doi:10.1038/nchembio.1845 We asked a collection of chemical biologists: "What would you say have been the most important historical contributions of chemical biology to broader areas of science"? Research Highlights Top Cell biology: Reversible Polo | Antibiotic resistance mechanisms: WTAs get tailored | Polymer biosynthesis: Rubber ramps up | Epigenomics: QC for ChIP | Peptides: A noncanonical conotoxin | Interactomics: Connecting the dots News and Views Top Metabolic engineering: Biosensor keeps DOPA on track   pp450 - 451 Pamela Peralta-Yahya doi:10.1038/nchembio.1830 Biosensors are emerging as an important tool to evolutionarily engineer metabolic pathway enzymes for the microbial production of chemicals. A colorimetric biosensor used to increase dopamine levels in yeast now enables the production of benzylisoquinoline alkaloids from glucose. See also: Article by DeLoache et al. Drug-target interactions: Stay tuned   pp451 - 452 Robert A Copeland doi:10.1038/nchembio.1831 The ability to vary a drug's residence time on a target is important for drug optimization. A series of reversible covalent inhibitors of select kinases demonstrates the feasibility of tuning residence time from minutes to days through modification of noncovalent features of the molecules. See also: Article by Bradshaw et al. Antifungal design: The toxicity-resistance yin-yang   pp453 - 454 David M Geiser doi:10.1038/nchembio.1838 A modified amphotericin antifungal that is less toxic to human cells, owing to its increased preference for its fungal ergosterol target versus human cholesterol, can still evade the evolution of resistance. See also: Article by Davis et al. mRNA regulation: A patch for a splice   pp454 - 455 Benjamin L Miller doi:10.1038/nchembio.1839 The spliceosome is an immensely complex molecular machine tasked with stitching together coding regions of genes. New work reveals how a small molecule can affect this machinery in a model of spinal muscular atrophy, a disease linked to aberrant splicing. See also: Article by Palacino et al. Biomaterials: Recipe for squid beak   pp455 - 456 Markus B Linder doi:10.1038/nchembio.1842 The molecular basis of biomaterial assembly and function can provide inspiration for new materials science designs. New research explains the squid beak's transition from soft to hard through the identification of two new families of proteins with unusual physical properties. See also: Article by Tan et al. Chemical Biology JOBS of the week Postdoctoral Scientist Ubiquitin-specific Proteases Structural Genomics Consortium (SGC) Postdoctoral Position University of California - San Francisco Postdoctoral Position in Biomedical Engineering University of Massachusetts Postdoctoral Fellowship Cleveland Clinic Lerner Research Institute PhD position Pathways of nanoparticle uptake and trafficking by cells (1.0 fte) Rijksuniversiteit Groningen More Science jobs from Chemical Biology EVENT Autumn School Chemical Biology 5-9 October 2015 Konstanz, Germany More science events from Perspective Top Biogenesis of reactive sulfur species for signaling by hydrogen sulfide oxidation pathways   pp457 - 464 Tatiana V Mishanina, Marouane Libiad and Ruma Banerjee doi:10.1038/nchembio.1834 Sulfide signaling is biologically important, but the identity and source of reactive sulfur species (RSS) remains unclear. An analysis of sulfur reactivity now suggests that oxidation pathways thought to dispose of sulfur may actually create RSS. Articles Top An enzyme-coupled biosensor enables (S)-reticuline production in yeast from glucose   pp465 - 471 William C DeLoache, Zachary N Russ, Lauren Narcross, Andrew M Gonzales, Vincent J J Martin et al. doi:10.1038/nchembio.1816 The biosynthesis of benzylisoquinoline alkaloids such as morphine requires tyrosine oxidases, which are prone to overoxidation. A colorimetric readout that co-opts betaxanthin enzymes now enables discovery of an improved oxidase that, with other enzymes, makes reticuline in yeast. See also: News and Views by Peralta-Yahya Chemical profiling of the genome with anti-cancer drugs defines target specificities   pp472 - 480 Baoxu Pang, Johann de Jong, Xiaohang Qiao, Lodewyk F A Wessels and Jacques Neefjes doi:10.1038/nchembio.1811 Topoisomerase inhibitors are genome-targeting drugs that induce DNA double-strand breaks or evict histones at sites of action. Genomic mapping of their target sites by ChIP-Seq and FAIRE-Seq and integration with ENCODE data identifies the target specificities of topoisomerase inhibitors and suggests ways to optimize their therapeutic properties. Nontoxic antimicrobials that evade drug resistance   pp481 - 487 Stephen A Davis, Benjamin M Vincent, Matthew M Endo, Luke Whitesell, Karen Marchillo et al. doi:10.1038/nchembio.1821 An amphotericin antifungal that is less toxic to human cells due to its increased capacity for binding the fungal ergosterol over the human cholesterol can still evade resistance mechanisms, challenging the resistance-toxicity yin-yang of antimicrobials. Chemical compounds See also: News and Views by Geiser Infiltration of chitin by protein coacervates defines the squid beak mechanical gradient   pp488 - 495 YerPeng Tan, Shawn Hoon, Paul A Guerette, Wei Wei, Ali Ghadban et al. doi:10.1038/nchembio.1833 The squid beak displays a 200-fold stiffness gradient across its length. A battery of experiments, including 'omics analysis and rheological measurements, now identifies two protein families that infiltrate and cross-link a porous chitin network to generate variable stiffness. See also: News and Views by Linder Efficient genetic encoding of phosphoserine and its nonhydrolyzable analog   pp496 - 503 Daniel T Rogerson, Amit Sachdeva, Kaihang Wang, Tamanna Haq, Agne Kazlauskaite et al. doi:10.1038/nchembio.1823 A newly engineered phosphoserine synthetase/tRNA pair allows quantitative insertion of phosphoserine or, when coupled with metabolic rewiring, a non-hydrolyzable analog into protein sequences, leading to high yields of modified constructs for functional analysis. Convergence of biological nitration and nitrosation via symmetrical nitrous anhydride   pp504 - 510 Dario A Vitturi, Lucia Minarrieta, Sonia R Salvatore, Edward M Postlethwait, Marco Fazzari et al. doi:10.1038/nchembio.1814 NO2- has been viewed primarily as a reservoir for NO and NO-modified species, activated by acids or metal catalysis. Isotopic labeling of NO and NO2- modifications in vitro and in vivo now demonstrates that NO2- also participates directly in these reactions through a symmetric N2O3 intermediate. SMN2 splice modulators enhance U1-pre-mRNA association and rescue SMA mice   pp511 - 517 James Palacino, Susanne E Swalley, Cheng Song, Atwood K Cheung, Lei Shu et al. doi:10.1038/nchembio.1837 A high-throughput screen identified a small molecule that promoted inclusion of SMN2 exon 7, increased SMN2 protein levels and extended survival in a SMA mouse model through stabilization of the interaction between SMN2 pre-mRNA and U1 snRNP complex. Chemical compounds See also: News and Views by Miller Structural mechanism underlying capsaicin binding and activation of the TRPV1 ion channel   pp518 - 524 Fan Yang, Xian Xiao, Wei Cheng, Wei Yang, Peilin Yu et al. doi:10.1038/nchembio.1835 A computational analysis of cryo-EM data defines the binding mode of capsaicin on TRPV1. A mutational analysis validates these findings, showing specific van der Waals and hydrogen-bonding interactions with the head, neck and tail regions of capsaicin. Chemical compounds Prolonged and tunable residence time using reversible covalent kinase inhibitors   pp525 - 531 J Michael Bradshaw, Jesse M McFarland, Ville O Paavilainen, Angelina Bisconte, Danny Tam et al. doi:10.1038/nchembio.1817 Structural changes in the capping groups of inverted cyanoacrylamide-based kinase inhibitors resulted in alterations in residence time, with some compounds exhibiting sustained pharmacological effects in vivo. Chemical compounds See also: News and Views by Copeland Errata Top Erratum: Carbohydrate anomalies in the PDB   p532 Jon Agirre, Gideon Davies, Keith Wilson and Kevin Cowtan doi:10.1038/nchembio0715-532a Erratum: Table of contents   p532 doi:10.1038/nchembio0715-532b 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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