Nature Chemical Biology Contents: February 2013 Volume 9 Number 2, pp 66 - 133

TABLE OF CONTENTS February 2013 Volume 9, Issue 2 Research Highlights News and Views Review Brief Communication Articles Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Reprint Collection on Epigenetics This collection of articles focuses on histone methylation, its links to human disease and the development of chemical modulators of histone methylation states as leads for chromatin-targeted drug discovery. Produced exclusively with support from:   Research Highlights Top Signaling: EGF, now on FM and AM | Mechanisms: Reduction deduction | Chemical ecology: Proline draws a diatom | Receptors: Insulin makes a move | Enzyme design: Going gluten-free | Cancer: Translocation, translocation, translocation | Lipids: Leaflets out of order | Plants: Making auxin News and Views Top Metabolism: Drug discovery goes for a swim   pp68 - 69 Jinkuk Choi and Peter Tontonoz doi:10.1038/nchembio.1167 Whole-organism screening is emerging as a promising alternative to cell-based assays, particularly for the study of processes that integrate information across cells and tissues. High-throughput screening of zebrafish larvae has enabled the discovery of small molecules that lower blood glucose levels and alleviate pathological symptoms in a mouse model of obesity and diabetes. Redox control: A black hole for oxidized glutathione   pp69 - 70 Jakob R Winther and Ursula Jakob doi:10.1038/nchembio.1161 There is a considerable amount of oxidized glutathione in living cells, yet it is virtually absent from the cytosol. The mystery of where it resides has now been solved. A study in baker's yeast revealed that oxidized glutathione is selectively stashed in vacuoles. Nuclear receptors: Oxysterols detour to neurodevelopment   pp70 - 71 Vania Broccoli and Massimiliano Caiazzo doi:10.1038/nchembio.1165 Cholic acid and 24(S),25-epoxycholesterol are oxysterols detected in the developing mesencephalic tissue and selectively regulate the production of either the red nucleus or dopaminergic neurons via activation of the liver X receptors. Chemical Biology JOBS of the week Postdoctoral, Physical / Chemical Cornell University Post-Doctoral Research Associate in Stem Cell Biology and iPS Disease Modelling Barts and the London School of Medicine & Dentistry, Queen Mary University of London PhD position in Evolutionary Biology, Developmental Biology and Systems Biology Isaac Salazar Ciudad PhD Position in Pollination Biology and Molecular Ecology Prof. Ian T. Baldwin, Department of Molecular Ecology, Max Plank Institute for Chemical Ecology Postdoctorat in Platelet Biology / Cell Signaling University of Liege - GIGA research center More Science jobs from Chemical Biology EVENT 4th International Conference for Young Chemists (ICYC) 30 January-1 February, 2013 Penang, Malaysia More science events from Review Top Metabolite damage and its repair or pre-emption   pp72 - 80 Carole L Linster, Emile Van Schaftingen and Andrew D Hanson doi:10.1038/nchembio.1141 Metabolites and cofactors can be converted to unwanted compounds by promiscuous enzymes and spontaneous chemical reactions. The growing list of enzymes that correct or prevent these reactions, akin to those that combat DNA and protein damage, have important roles in maintaining homeostasis and preventing disease. Brief Communication Top Structure and dynamics of a primordial catalytic fold generated by in vitro evolution   pp81 - 83 Fa-An Chao, Aleardo Morelli, John C Haugner III, Lewis Churchfield, Leonardo N Hagmann, Lei Shi, Larry R Masterson, Ritimukta Sarangi, Gianluigi Veglia and Burckhard Seelig doi:10.1038/nchembio.1138 Structural characterization of an artificial zinc-dependent enzyme created by in vitro evolution yields a new, flexible fold that challenges straightforward definitions of active site residues and raises questions about protein evolution. Articles Top Small-molecule activation of the TRAIL receptor DR5 in human cancer cells   pp84 - 89 Gelin Wang, Xiaoming Wang, Hong Yu, Shuguang Wei, Noelle Williams, Daniel L Holmes, Randal Halfmann, Jacinth Naidoo, Lai Wang, Lin Li, She Chen, Patrick Harran, Xiaoguang Lei and Xiaodong Wang doi:10.1038/nchembio.1153 Bioymifi, a small-molecule death receptor 5 (DR5) agonist, induces selective cancer cell apoptosis as a single agent or in synergy with small-molecule Smac mimetics. Chemical compounds Allosteric regulation of DegS protease subunits through a shared energy landscape   pp90 - 96 Randall V Mauldin and Robert T Sauer doi:10.1038/nchembio.1135 Allosteric conformations and proteolytic activities of each subunit of the trimeric E. coli DegS protease share a cooperatively coupled energy landscape that allows regulation via the binding of substrate and OMP peptides. Whole-organism screening for gluconeogenesis identifies activators of fasting metabolism   pp97 - 104 Philipp Gut, Bernat Baeza-Raja, Olov Andersson, Laura Hasenkamp, Joseph Hsiao, Daniel Hesselson, Katerina Akassoglou, Eric Verdin, Matthew D Hirschey and Didier Y R Stainier doi:10.1038/nchembio.1136 Maintaining energy homeostasis requires complex feedback across organs that is difficult to study in isolated systems. New research uses whole-organism screening to identify key regulators of fasting metabolism in zebrafish, including ligands for the mitochondrial transporter protein TSPO. A cyclic form of N6-threonylcarbamoyladenosine as a widely distributed tRNA hypermodification   pp105 - 111 Kenjyo Miyauchi, Satoshi Kimura and Tsutomu Suzuki doi:10.1038/nchembio.1137 N6-Threonylcarbamoyladenosine (t6A), a modified nucleotide found in certain tRNAs, has an essential role in translational fidelity. New analytical data reveal that t6A adopts a cyclic form (ct6A) in cells and has led to the identification of the enzymes that convert t6A to ct6A. Chemical compounds Activation of Hsp70 reduces neurotoxicity by promoting polyglutamine protein degradation   pp112 - 118 Adrienne M Wang, Yoshinari Miyata, Susan Klinedinst, Hwei-Ming Peng, Jason P Chua, Tomoko Komiyama, Xiaokai Li, Yoshihiro Morishima, Diane E Merry, William B Pratt, Yoichi Osawa, Catherine A Collins, Jason E Gestwicki and Andrew P Lieberman doi:10.1038/nchembio.1140 An allosteric activator of Hsp70 mimics Hip and reduces neurotoxicity in a model for spinobulbar muscular atrophy by promoting ubiquitination and degradation of oligomeric polyglutamine-containing clients. Chemical compounds Multiple glutathione disulfide removal pathways mediate cytosolic redox homeostasis   pp119 - 125 Bruce Morgan, Daria Ezeriņa, Theresa N E Amoako, Jan Riemer, Matthias Seedorf and Tobias P Dick doi:10.1038/nchembio.1142 Quantification of cytosolic glutathione redox potential leads to the discovery that the ABC-C transporter Ycf1 rapidly transports oxidized glutathione (GSSG) into vacuoles and whole-cell GSSG should not be used as a proxy for cytosolic GSSG. Brain endogenous liver X receptor ligands selectively promote midbrain neurogenesis   pp126 - 133 Spyridon Theofilopoulos, Yuqin Wang, Satish Srinivas Kitambi, Paola Sacchetti, Kyle M Sousa, Karl Bodin, Jayne Kirk, Carmen Saltó, Magnus Gustafsson, Enrique M Toledo, Kersti Karu, Jan-Åke Gustafsson, Knut R Steffensen, Patrik Ernfors, Jan Sjövall, William J Griffiths and Ernest Arenas doi:10.1038/nchembio.1156 Cholic acid and 24(S),25-epoxycholesterol are endogenous midbrain LXR ligands that are neurogenic for red nucleus or dopaminergic neurons, respectively. Top Advertisement Subscribe today to Nature Chemical Biology Reflecting the diversity and excitement of chemical biology research. Subscribe online here today: https://secure.nature.com/subscribe/nchembio   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. 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