Nature Chemical Biology Contents: May 2013 Volume 9 Number 5, pp 285 - 343

TABLE OF CONTENTS May 2013 Volume 9, Issue 5 Commentary Research Highlights News and Views Brief Communication Articles Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement NPG and Frontiers form alliance to further open science Frontiers is at the forefront of building the ultimate Open Science platform and is driving innovations around peer-review, article and author impact metrics and social networking for researchers. NPG and Frontiers will work together to empower researchers to change the way science is communicated. Find out more here   Commentary Top Biocatalytic retrosynthesis   pp285 - 288 Nicholas J Turner and Elaine O'Reilly doi:10.1038/nchembio.1235 The recent development of a broad range of biocatalysts that can be applied in organic synthesis has brought into focus the need to rethink the way in which organic target molecules might be constructed in the future. To aid synthetic chemists in identifying where biocatalysts might be usefully applied, we propose that guidelines and rules for 'biocatalytic retrosynthesis' be developed and that this new approach be embedded in the future training and education of organic chemists. Research Highlights Top Drug resistance: In the niche | Chemical ecology: Caffeine buzz | Synthetic biology: Make mine decaf | Viral infection: Influenza loses to a lipid | Leukemia: PHFriends with RAR | Peptidoglycan: Rip it up | Protein interactions: PLATO's molecular dialog | Drug discovery: Stolen isoprenoids News and Views Top Microbiology: Plan B for quorum sensing   pp292 - 293 Ajai A Dandekar and E. Peter Greenberg doi:10.1038/nchembio.1233 Pseudomonas aeruginosa uses several intertwined cell-cell communication systems, called quorum sensing (QS) systems, to control gene expression. A QS signal-dependent transcription factor called LasR is at the top of the network. Mutations in lasR inactivate QS, but a new study has revealed an alternate signaling pathway that allows Pseudomonas aeruginosa to bypass LasR and activate a subset of quorum-controlled genes in times of stress. See also: Article by Ulanovskaya et al. Metabolism: Cancer mistunes methylation   pp293 - 294 Tomer Shlomi and Joshua D Rabinowitz doi:10.1038/nchembio.1234 Metabolic aberrations affecting protein and DNA methylation are a potential source of cancer. A new study shows that the metabolic enzyme nicotinamide N-methyl-transferase, which is overexpressed in several types of tumors, can enhance cancer aggressiveness by draining methyl groups from S-adenosyl-methionine. Biosynthesis: Metal matters   pp295 - 296 John Hugh Snyder and Xiaoquan Qi doi:10.1038/nchembio.1232 A study of an insect prenyltransferase demonstrates that the product specificity of this bifunctional enzyme can be regulated by the presence of different divalent metal cofactors, resulting, for example, in the production of the precursors for either insect defense compounds or developmental hormones. See also: Article by Lee et al. Chemical Biology JOBS of the week Postdoctoral fellowship in chemical biology Mount Sinai School of Medicine More Science jobs from Brief Communication Top Atomic-resolution monitoring of protein maturation in live human cells by NMR   pp297 - 299 Lucia Banci, Letizia Barbieri, Ivano Bertini, Enrico Luchinat, Erica Secci, Yuguang Zhao and A Radu Aricescu doi:10.1038/nchembio.1202 Analysis of proteins within their native environment can confirm and extend in vitro–derived conclusions. NMR analysis of superoxide dismutase 1 in live human cells now corroborates previously identified steps on the maturation pathway and demonstrates copper-independent function of the chaperone CCS. Articles Top NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink   pp300 - 306 Olesya A Ulanovskaya, Andrea M Zuhl and Benjamin F Cravatt doi:10.1038/nchembio.1204 NNMT converts SAM to the stable metabolite 1-methylnicotinamide, which reduces the methylation potential of cancer cells and thereby alters their epigenetic state to heighten the expression of protumorigenic genes. See also: News and Views by Dandekar & Greenberg ATP-competitive inhibitors block protein kinase recruitment to the Hsp90-Cdc37 system   pp307 - 312 Sigrun Polier, Rahul S Samant, Paul A Clarke, Paul Workman, Chrisostomos Prodromou and Laurence H Pearl doi:10.1038/nchembio.1212 ATP-competitive inhibitors compete with the Hsp90 cochaperone Cdc37 for the ATP site in kinases, depriving kinases of access to protein quality control machinery and promoting their degradation. Thus, in addition to inhibiting the catalytic activity of kinases, ATP-competitive inhibitors can reduce the number of active kinases in a cell by promoting their degradation. A single-molecule dissection of ligand binding to a protein with intrinsic dynamics   pp313 - 318 Eunkyung Kim, Sanghwa Lee, Aram Jeon, Jung Min Choi, Hee-Seung Lee, Sungchul Hohng and Hak-Sung Kim doi:10.1038/nchembio.1213 Proteins that sample multiple conformations in the absence of a ligand have been presumed to operate via a conformational selection mechanism. Single molecule FRET studies of maltose binding protein now cast doubts on that assumption. Chemical compounds Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group   pp319 - 325 Mercedes Lobera, Kevin P Madauss, Denise T Pohlhaus, Quentin G Wright, Mark Trocha, Darby R Schmidt, Erkan Baloglu, Ryan P Trump, Martha S Head, Glenn A Hofmann, Monique Murray-Thompson, Benjamin Schwartz, Subhas Chakravorty, Zining Wu, Palwinder K Mander, Laurens Kruidenier, Robert A Reid, William Burkhart, Brandon J Turunen, James X Rong, Craig Wagner, Mary B Moyer, Carrow Wells, Xuan Hong, John T Moore, Jon D Williams, Dulce Soler, Shomir Ghosh and Michael A Nolan doi:10.1038/nchembio.1223 Class IIa histone deacetylases (HDACs) are generally viewed as noncatalytic readers of acetylated lysines within proteins. Specific inhibitors of class IIa HDACs, based on a new zinc-binding scaffold, offer chemical probes to explore the biological function and potential druggability of this enzyme subclass. Chemical compounds Ligand-binding dynamics rewire cellular signaling via estrogen receptor-α    pp326 - 332 Sathish Srinivasan, Jerome C Nwachukwu, Alex A Parent, Valerie Cavett, Jason Nowak, Travis S Hughes, Douglas J Kojetin, John A Katzenellenbogen and Kendall W Nettles doi:10.1038/nchembio.1214 Constrained ligands activate a canonical ER pathway via a common structural mechanism, whereas dynamic ligands rewire the canonical pathway; DBD-dependent activity interferes with canonical ER proliferative signals and associates with a strong anti-inflammatory effect. Chemical compounds Two Fe-S clusters catalyze sulfur insertion by radical-SAM methylthiotransferases   pp333 - 338 Farhad Forouhar, Simon Arragain, Mohamed Atta, Serge Gambarelli, Jean-Marie Mouesca, Munif Hussain, Rong Xiao, Sylvie Kieffer-Jaquinod, Jayaraman Seetharaman, Thomas B Acton, Gaetano T Montelione, Etienne Mulliez, John F Hunt and Marc Fontecave doi:10.1038/nchembio.1229 Methylthiolation by radical SAM enzymes is thought to include the sacrificial breakdown of a second Fe-S cluster to generate the sulfur cosubstrate. A biochemical, spectroscopic and structural study of two methylthiotransferases shows these enzymes retain their clusters, using exogenous thiols to modify their targets. A cell-cell communication signal integrates quorum sensing and stress response   pp339 - 343 Jasmine Lee, Jien Wu, Yinyue Deng, Jing Wang, Chao Wang, Jianhe Wang, Changqing Chang, Yihu Dong, Paul Williams and Lian-Hui Zhang doi:10.1038/nchembio.1225 IQS is a Pseudomonas aeruginosa quorum sensing molecule that functions during phosphate limitation and lies near the top of the QS signaling hierarchy. Chemical compounds See also: News and Views by Snyder & Qi Top Advertisement Nature Chemical Biology Focus on Targets This Focus issue tackles challenges in the discovery and validation of new targets for clinical purposes, explores how chemical probes and tools facilitate our understanding of the relationship between targets and biology and allow researchers to expand target space. Access this Focus for free at www.nature.com/nchembio/focus/targets   Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. 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