Nature Chemical Biology Contents: February 2014 Volume 10 Number 2 pp 85 - 164

If you are unable to see the message below, click here to view.

Advertisement Frontiers in Molecular Biosciences is a new, open access journal launching in 2014! We are currently building an outstanding editorial board of researchers from across the globe. We need world class scientists like you to be part of a journal driven and directed by working scientists, for working scientists. Read more about how you can be part of the future of research publication TABLE OF CONTENTS February 2014 Volume 10, Issue 2 Editorial Research Highlights News and Views Brief Communications Articles Corrigenda Erratum Subscribe   Facebook   RSS   Recommend to library   Twitter   Editorial Top Put your thinking caps on   p85 doi:10.1038/nchembio.1454 Opportunities abound for chemical biologists to contribute to global initiatives designed to unlock the secrets of the human brain. Research Highlights Top Drug repurposing: Down goes Ikaros | Microbial pathogenesis: Mtb takes a Trp | Metabolism: Brucei's next top model | Neurotransmitters: Glutamate gets fat | RNA structure: Folding in the wild | Channels: Dual eicosanoid activity | Translation: Makes sense | Target identification: Chemical landing pad News and Views Top Metalloproteins: A new face for biomass breakdown   pp88 - 89 Shinya Fushinobu doi:10.1038/nchembio.1434 Lytic polysaccharide mono-oxygenases oxidatively cleave the glycosidic chain on the crystalline surface of cellulose or chitin to create an entry point for hydrolytic cellulases or chitinases. The discovery of a new family of lytic polysaccharide mono-oxygenases expands the possibilities for the use of these enzymes to accelerate biomass degradation. See also: Article by Hemsworth et al. Cancer therapy: Altering mitochondrial properties   pp89 - 90 Paolo Pinton and Guido Kroemer doi:10.1038/nchembio.1440 The mitochondrial permeability transition pore (mPTP) is a multiprotein complex that regulates cell death in multiple pathological conditions. The discovery of new critical components of the mPTP and the identification of anticancer drugs acting on mPTP opens new frontiers for mitochondrial medicine. See also: Article by Wang et al. Regenerative medicine: Of fish and men   pp91 - 92 Thomas A Rando doi:10.1038/nchembio.1449 Stem cell therapeutics hold great promise, but obtaining optimal cell populations for transplantation remains a major challenge. High-throughput screens of zebrafish embryonic cells have enabled identification of small molecules that can direct the fate of pluripotent stem cells toward tissue-specific progenitors with high therapeutic potential. Chemical Biology JOBS of the week Post Doctoral Stipend in Co-Infection biology Lund University Junior Research Group leader Computational Biology Saarland University Epigenetics and Stem Cell Biology Max Planck Institute for Heart and Lung Research Postdoctoral Position in Epigenetics / Cancer Biology MPI Bad Nauheim Research Fellow- T Cell Receptor Biology Dana-Farber Cancer Institute (DFCI) More Science jobs from Chemical Biology EVENT Chemical Biology Discussion Group Year-End Symposium 3 June, 2014 New York, USA More science events from Brief Communications Top A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation   pp93 - 95 Jianzhao Liu, Yanan Yue, Dali Han, Xiao Wang, Ye Fu et al. doi:10.1038/nchembio.1432 Certain adenosine residues within mammalian RNAs undergo reversible N6 methylation. Two methyltransferase enzymes, METTL3 and METTL14, as well as the splicing factor WTAP are identified as core components of the multiprotein complex that deposits RNA N6-methyladenosine (m6A) in nuclear RNAs. Chemical compounds Pyridomycin bridges the NADH- and substrate-binding pockets of the enoyl reductase InhA   pp96 - 98 Ruben C Hartkoorn, Florence Pojer, Jon A Read, Helen Gingell, João Neres et al. doi:10.1038/nchembio.1405 Crystal structures reveal that the antitubercular compound pyridomycin blocks binding of the NADH cofactor to the fatty acid synthesis enzyme InhA while also blocking the lipid substrate–binding pocket. Articles Top Genomic mining of prokaryotic repressors for orthogonal logic gates   pp99 - 105 Brynne C Stanton, Alec A K Nielsen, Alvin Tamsir, Kevin Clancy, Todd Peterson et al. doi:10.1038/nchembio.1411 In synthetic biology designs, circuit components can generally move within the cell, meaning that functional cross-talk can cause faulty wiring. Genome mining, synthetic promoter construction and cross-reactivity screening now identify 20 orthogonal TetR repressor-promoter pairs for use in complex applications. Radical SAM enzyme QueE defines a new minimal core fold and metal-dependent mechanism   pp106 - 112 Daniel P Dowling, Nathan A Bruender, Anthony P Young, Reid M McCarty, Vahe Bandarian et al. doi:10.1038/nchembio.1426 Crystal structures of QueE, a radical SAM enzyme that converts the purine base of GTP into a deazapurine found in natural products and tRNA, explain how the enzyme functions with a trimmed-down radical SAM enzyme fold and rationalizes its unusual Mg2+ dependency. Integrated phenotypic and activity-based profiling links Ces3 to obesity and diabetes   pp113 - 121 Eduardo Dominguez, Andrea Galmozzi, Jae Won Chang, Ku-Lung Hsu, Joanna Pawlak et al. doi:10.1038/nchembio.1429 Phenotypic screening for serine hydrolase inhibitors capable of modulating lipid storage coupled with target deconvolution identifies carboxylesterase 3 as having a role in regulating adipocyte function, with enzyme inhibition causing positive outcomes in mouse models of obesity and diabetes. Chemical compounds Discovery and characterization of a new family of lytic polysaccharide monooxygenases   pp122 - 126 Glyn R Hemsworth, Bernard Henrissat, Gideon J Davies and Paul H Walton doi:10.1038/nchembio.1417 Use of a domain of unknown function as the input for bioinformatic searching reveals a new Cu-dependent family of chitinases, assigned as CAZy group AA11, that diverge in sequence but share structural homology with the existing AA9 and AA10 families. See also: News and Views by Fushinobu A conserved water-mediated hydrogen bond network defines bosutinib's kinase selectivity   pp127 - 132 Nicholas M Levinson and Steven G Boxer doi:10.1038/nchembio.1404 Crystallographic analysis and spectroscopic studies employing the nitrile moiety of bosutinib as an IR-active probe reveal that structured water molecules, organized by the gatekeeper residues of kinases, mediate the selectivity profile of kinase inhibitor binding. Orphan nuclear receptor TR3 acts in autophagic cell death via mitochondrial signaling pathway   pp133 - 140 Wei-jia Wang, Yuan Wang, Hang-zi Chen, Yong-zhen Xing, Feng-wei Li et al. doi:10.1038/nchembio.1406 TR3 is an orphan nuclear receptor with roles in apoptosis. A TR3-binding compound induces mitochondrial translocation of TR3 and autophagy via the Nix–Toms–ANT1/VDAC1 pathway, providing a mechanism for cell death in melanoma cells that are resistant to spontaneous and drug-induced apoptosis. Chemical compounds See also: News and Views by Pinton & Kroemer VMAT2 identified as a regulator of late-stage β-cell differentiation   pp141 - 148 Daisuke Sakano, Nobuaki Shiraki, Kazuhide Kikawa, Taiji Yamazoe, Masateru Kataoka et al. doi:10.1038/nchembio.1410 A screen for compounds that promote ES cell differentiation into pancreatic β cells identified a VMAT2- and monoamine-dependent suppression mechanism of pancreatic β-cell differentiation. VMAT2 inhibitors potentiated differentiation from Pdx1-positive pancreatic progenitor cells into Ngn3-positive endocrine precursors, and then into β cells with increased insulin production. Protonation drives the conformational switch in the multidrug transporter LmrP   pp149 - 155 Matthieu Masureel, Chloé Martens, Richard A Stein, Smriti Mishra, Jean-Marie Ruysschaert et al. doi:10.1038/nchembio.1408 Substrate binding to the multidrug exporter LmrP from Lactococcus lactis catalyzes proton entrance by stabilizing an outward-open conformation. Transitions between conformational states are dictated by proton passage down the transmembrane helical bundle. E2 enzyme inhibition by stabilization of a low-affinity interface with ubiquitin   pp156 - 163 Hao Huang, Derek F Ceccarelli, Stephen Orlicky, Daniel J St-Cyr, Amy Ziemba et al. doi:10.1038/nchembio.1412 In the ubiquitin-proteasome system, E2 enzymes such as Cdc34A mediate the transfer of ubiquitin to protein substrates, which are thus marked for proteasomal degradation or other fates. New structural data reveal that the small-molecule inhibitor CC0651 impairs Cdc34A activity by stabilizing the normally transient Cdc34A–ubiquitin complex. Chemical compounds Corrigenda Top Corrigendum: Mycobacterium tuberculosis nitrogen assimilation and host colonization require aspartate   p164 Alexandre Gouzy, Gerald Larrouy-Maumus, Ting-Di Wu, Antonio Peixoto, Florence Levillain et al. doi:10.1038/nchembio0214-164a Corrigendum: Elementary tetrahelical protein design for diverse oxidoreductase functions   p164 Tammer A Farid, Goutham Kodali, Lee A Solomon, Bruce R Lichtenstein, Molly M Sheehan et al. doi:10.1038/nchembio0214-164b Corrigendum: A serine-substituted P450 catalyzes highly efficient carbene transfer to olefins in vivo   p164 Pedro S Coelho, Z Jane Wang, Maraia E Ener, Stefanie A Baril, Arvind Kannan et al. doi:10.1038/nchembio0214-164d Erratum Top Erratum: What's up 'Doc'?   p164 Wolfgang Peti and Rebecca Page doi:10.1038/nchembio0214-164c 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

You have been sent this Table of Contents Alert because you have opted in to receive it. You can change or discontinue your e-mail alerts at any time, by modifying your preferences on your nature.com account at: www.nature.com/myaccount (You will need to log in to be recognised as a nature.com registrant) For further technical assistance, please contact our registration department For print subscription enquiries, please contact our subscription department For other enquiries, please contact our customer feedback department Nature Publishing Group | 75 Varick Street, 9th Floor | New York | NY 10013-1917 | USA Nature Publishing Group's worldwide offices: London - Paris - Munich - New Delhi - Tokyo - Melbourne San Diego - San Francisco - Washington - New York - Boston Macmillan Publishers Limited is a company incorporated in England and Wales under company number 785998 and whose registered office is located at Brunel Road, Houndmills, Basingstoke, Hampshire RG21 6XS. © 2014 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.