Nature Chemical Biology Contents: May 2017, Volume 13 No 6 pp 559 - 691

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Advertisement nature.com webcasts Springer Nature presents a custom webcast on: 3D High-Content Screening of Organoids for Drug Discovery.  Register for FREE Date: Wednesday 24th May Time: 8AM PDT | 11AM EDT | 4PM BST | 5PM CEST Sponsored by: Perkin Elmer  www.PerkinElmer.com/cellularimaging TABLE OF CONTENTS June 2017 Volume 13, Issue 6 Editorial Commentaries Research Highlights News and Views Perspectives Review Brief Communications Articles Errata Corrigendum Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement The 1st Symposium on Nucleic Acid Modifications will bring together key players in the previously segregated fields of RNA and DNA modifications, which are now merging to create a brand new interdisciplinary research field that includes chemical biology, structural biology, bioinformatics, biophysics and cell biology, developmental biology and epigenetics. The symposium will outline the major developments in this rapidly developing field, and includes talks from leaders in this exciting area of study. www.imb.de/2017nucmod     Focus Top Focus on Chemical approaches in developmental biology The development of model organisms such as zebrafish and worms progresses from a single cell to tissues and organs. In this issue, a collection of articles highlights advances and opportunities at the intersection of developmental and chemical biology. Focus on Chemical approaches in developmental biology Editorial Top Shaping embryonic development   p559 doi:10.1038/nchembio.2403 The growing intersection between chemical tools and principles and developmental biology is providing new insights into the molecular-level details of developmental processes. Commentaries Top Small-molecule phenotypic screening with stem cells   pp560 - 563 Andrei Ursu, Hans R Scholer and Herbert Waldmann doi:10.1038/nchembio.2383 To fully leverage the potential of human-induced pluripotent stem cells (hiPSCs), improved and standardized reprogramming methods and large-scale collections of hiPSC lines are needed, and the stem cell community must embrace chemical biology methodology for target identification and validation. Unraveling cell-to-cell signaling networks with chemical biology   pp564 - 568 Zev J Gartner, Jennifer A Prescher and Luke D Lavis doi:10.1038/nchembio.2391 Cell-to-cell signaling networks, although poorly understood, guide tissue development, regulate tissue function and may become dysregulated in disease. Chemical biologists can develop the next generation of tools to untangle these complex and dynamic networks of interacting cells. Research Highlights Top Synthetic biology: Return to sender | Enzymology: Radical ring resizing | Infectious disease: A lethal sugar fix | Plant development: Get lit on steroids News and Views Top Signal Transduction: Notch catches a Jagged edge   pp570 - 571 Stephen C Blacklow doi:10.1038/nchembio.2379 Notch signaling is an essential cell-cell communication pathway that influences numerous cell fate decisions during development. Structural and biochemical studies of a Notch-Jagged complex dramatically advance current understanding of ligand recognition, and reveal evidence of catch-bond behavior in the complex. Immunology: Mind the immuno-connection gap   pp572 - 573 Wolfgang Link doi:10.1038/nchembio.2373 Biologic drugs that modulate the immune system have revolutionized the therapeutic landscape for several selected cancer types. A new study reports an image-based assay system to monitor cell-cell interactions, identifying small-molecule compounds with immunomodulatory capacity. See also: Article by Vladimer et al. Optogenetics: Switching with red and blue   pp573 - 574 Fuun Kawano, Fan Shi and Masayuki Yazawa doi:10.1038/nchembio.2387 Multiple optogenetic technologies are required to control biological activity simultaneously with different colors of light. Optimizing a near-infrared-induced heterodimerization system, which can be combined with blue-light-controlled domains, enables precise spatiotemporal control of target molecules in live mammalian cells. See also: Article by Redchuk et al. Protein degradation: DCAFinating splicing   pp575 - 576 Georg E Winter doi:10.1038/nchembio.2378 Chemical control of protein homeostasis and induction of protein destabilization are emerging therapeutic strategies. Two recent studies identify a set of sulfonamides that can modulate the CRL4DCAF15 E3 ligase complex to target the splicing factor RBM39 for proteasomal degradation. See also: Article by Uehara et al. Nature Chemical Biology JOBS of the week Postdoctoral position in chemical biology Ecole Normale Superieure (ENS Paris) PhD position in chemical biology Ecole Normale Superieure (ENS Paris) Postdoctoral The Scripps Research Institute Full-time Faculty Position in Earth System Science Universidad del Rosario, Bogotá Colombia Multiple Faculty Positions at ShanghaiTech University ShanghaiTech University More Science jobs from Nature Chemical Biology EVENT World Congress on Marine Science 16 - 17 November 2017 Atlanta, USA More science events from Perspectives Top Small-molecule pheromones and hormones controlling nematode development   pp577 - 586 Rebecca A Butcher doi:10.1038/nchembio.2356 Illuminating developmental biology through photochemistry   pp587 - 598 Lukasz Kowalik and James K Chen doi:10.1038/nchembio.2369 Review Top The perception of strigolactones in vascular plants   pp599 - 606 Shelley Lumba, Duncan Holbrook-Smith and Peter McCourt doi:10.1038/nchembio.2340 Brief Communications Top CRISPR-Cas9 strategy for activation of silent Streptomyces biosynthetic gene clusters   pp607 - 609 Mingzi M Zhang, Fong Tian Wong, Yajie Wang, Shangwen Luo, Yee Hwee Lim et al. doi:10.1038/nchembio.2341 Most microbial biosynthetic gene clusters are inactive under laboratory culture conditions. A CRISPR-Cas9 genome-editing approach in Streptomyces species enables the targeted activation of silent gene clusters and production of encoded natural products. Chemical compounds Structural and functional insight into human O-GlcNAcase   pp610 - 612 Christian Roth, Sherry Chan, Wendy A Offen, Glyn R Hemsworth, Lianne I Willems et al. doi:10.1038/nchembio.2358 Crystal structures of human O-GlcNAc hydrolase (hOGA) fragments show that hOGA's dimeric structure is organized by swapping of an α-helical element and reveal features of inhibitor binding to the catalytic domain. Insights into activity and inhibition from the crystal structure of human O-GlcNAcase   pp613 - 615 Nathaniel L Elsen, Sangita B Patel, Rachael E Ford, Dawn L Hall, Fred Hess et al. doi:10.1038/nchembio.2357 Crystallographic analysis of human O-GlcNAc hydrolase (hOGA) fragments containing the catalytic domain, including structures in complex with known inhibitors, suggests that OGA is functional as a dimer and defines opportunities for structure-based drug design. Articles Top Chemical screening identifies ATM as a target for alleviating senescence   pp616 - 623 Hyun Tae Kang, Joon Tae Park, Kobong Choi, Yongsub Kim, Hyo Jei Claudia Choi et al. doi:10.1038/nchembio.2342 Ataxia telangiectasia mutated (ATM) directly interacts with and phosphorylates the V-ATPase V1 subunit ATP6V1G1, thereby decreasing V1-V0 assembly in the V-ATPase. Attenuation of ATM activity results in lysosomal pH acidification, recovery of autophagy and alleviation of senescence. Diabetes reversal by inhibition of the low-molecular-weight tyrosine phosphatase   pp624 - 632 Stephanie M Stanford, Alexander E Aleshin, Vida Zhang, Robert J Ardecky, Michael P Hedrick et al. doi:10.1038/nchembio.2344 The generation of low-molecular-weight protein tyrosine phosphatase (LMPTP) knockout mice combined with the identification of a small-molecule uncompetitive LMPTP inhibitor reveals a role for LMPTP in regulating insulin resistance. Chemical compounds Near-infrared optogenetic pair for protein regulation and spectral multiplexing   pp633 - 639 Taras A Redchuk, Evgeniya S Omelina, Konstantin G Chernov and Vladislav V Verkhusha doi:10.1038/nchembio.2343 The engineering of Q-PAS1, a single-domain variant of PpsR2, led to an optimized optogenetic system based on the Q-PAS1-BphP1 interaction, which was applied to the regulation of transcription, epigenetic state and protein localization by near-infrared light. AtaT blocks translation initiation by N-acetylation of the initiator tRNAfMet   pp640 - 646 Dukas Jurenas, Sneha Chatterjee, Albert Konijnenberg, Frank Sobott, Louis Droogmans et al. doi:10.1038/nchembio.2346 Characterization of an enterohaemorrhagic E. coli toxin-antitoxin system reveals that the toxin AtaT specifically acetylates Met-tRNAfMet at the methionyl amine, making it incompetent for translation initiation, which inhibits translation. Phosphorylated glycosphingolipids essential for cholesterol mobilization in Caenorhabditis elegans   pp647 - 654 Sebastian Boland, Ulrike Schmidt, Vyacheslav Zagoriy, Julio L Sampaio, Raphael F Fritsche et al. doi:10.1038/nchembio.2347 mmPEGC-C22 is a nonsterol glycolipid involved in early Caenorhabditis elegans larval development that can rescue the growth-arrest phenotype caused by sterol deficiency and is controlled by TGF-β to help mobilize internal sterol pools. Chemical compounds Mechanistic insights into energy conservation by flavin-based electron bifurcation   pp655 - 659 Carolyn E Lubner, David P Jennings, David W Mulder, Gerrit J Schut, Oleg A Zadvornyy et al. doi:10.1038/nchembio.2348 Structural analysis and spectroscopy elucidate how pairs of electrons are bifurcated in a flavoenzyme by generating an unstable flavin semiquinone, thus coupling exergonic and endergonic oxidation-reduction reactions. Using the pimeloyl-CoA synthetase adenylation fold to synthesize fatty acid thioesters   pp660 - 667 Menglu Wang, Lucile Moynie, Peter J Harrison, Van Kelly, Andrew Piper et al. doi:10.1038/nchembio.2361 Structures of pimeloyl-CoA synthetase (BioW) provide insights into its catalytic mechanism and how it selects the correct length of dicarboxylic acid substrate, guiding engineering to make the enzyme capable of producing alternative CoA products. Chemical compounds See also: Article by Estrada et al. The pimeloyl-CoA synthetase BioW defines a new fold for adenylate-forming enzymes   pp668 - 674 Paola Estrada, Miglena Manandhar, Shi-Hui Dong, Jaigeeth Deveryshetty, Vinayak Agarwal et al. doi:10.1038/nchembio.2359 Structural analysis of pimeloyl-CoA synthetase (BioW) provides insight into how the enzyme ensures proper substrate positioning and how a key residue ensures proofreading of the reaction through hydrolysis of noncognate adenylated substrates. Chemical compounds See also: Article by Wang et al. Selective degradation of splicing factor CAPERα by anticancer sulfonamides   pp675 - 680 Taisuke Uehara, Yukinori Minoshima, Koji Sagane, Naoko Hata Sugi, Kaoru Ogawa Mitsuhashi et al. doi:10.1038/nchembio.2363 A series of sulfonamides induced the ubiquitin-mediated degradation of the U2AF-related splicing factor, coactivator of activating protein-1 and estrogen receptor α (CAPERα), by promoting direct binding between CAPERα and the CRL4 substrate receptor DCAF15. Chemical compounds Global survey of the immunomodulatory potential of common drugs   pp681 - 690 Gregory I Vladimer, Berend Snijder, Nikolaus Krall, Johannes W Bigenzahn, Kilian V M Huber et al. doi:10.1038/nchembio.2360 A high-content screening platform that measures the immunological potential of small-molecule and biologic drugs by computationally determining changes in the physical interactions among peripheral mononuclear leukocytes revealed known immunomodulators and also approved drugs as regulators of unexpected targets, including MST1R. Corrigendum Top Corrigendum: Full antagonism of the estrogen receptor without a prototypical ligand side chain   p691 Sathish Srinivasan, Jerome C Nwachukwu, Nelson E Bruno, Venkatasubramanian Dharmarajan, Devrishi Goswami et al. doi:10.1038/nchembio0617-691c Errata Top Erratum: A Vibrio cholerae autoinducer-receptor pair that controls biofilm formation   p691 Kai Papenfort, Justin E Silpe, Kelsey R Schramma, Jian-Ping Cong, Mohammad R Seyedsayamdost et al. doi:10.1038/nchembio0617-691a Erratum: Full antagonism of the estrogen receptor without a prototypical ligand side chain   p691 Sathish Srinivasan, Jerome C Nwachukwu, Nelson E Bruno, Venkatasubramanian Dharmarajan, Devrishi Goswami et al. doi:10.1038/nchembio0617-691b 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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