Nature Chemical Biology Contents: November 2011 Volume 7 pp756-853

Advertisement Do you need to know drug molecule protein interactions? Then check our new publication in Proteomics 2011 "SAHA Capture Compound - A novel tool for the profiling of histone deacetylases and the identification of additional vorinostat binders". TABLE OF CONTENTS November 2011 Volume 7, Issue 11 Research Highlights News and Views Brief Communications Articles Corrigendum Research Highlights Top Stem cells: Oxidative renewal | Metalloenzymes: Copper chews on cellulose | Drug discovery: Sidelining c-Myc | Malaria: An addiction to isoprenoids | Channels: GRASPing CFTR | Olfaction: A DEET-induced confusion | Biosynthesis: Finding pheofungins | Protein folding: Gamers see the solution News and Views Top Carbohydrates: Cracking the glycan sequence code pp758 - 759 Christopher J Jones and Cynthia K Larive doi:10.1038/nchembio.696 For years scientists have debated whether glycans, like DNA, RNA and proteins, have a true sequence. In a recent study, researchers show that the proteoglycan bikunin has a defined and predictable sequence, opening the door for a new understanding of the glycome. Full Text | PDF See also: Article by Ly et al. Ion channels: Manipulating the munchies in mice pp759 - 760 Myles H Akabas doi:10.1038/nchembio.697 Crystal structure and drug pharmacophore structure-activity data guided a combined mutagenesis and chemical screen to develop ligand-gated ion channels activated by unique chemical agonists. Through genetic engineering, these channels can be used to manipulate neuronal excitability and dissect the neuronal circuitry responsible for complex behaviors. Full Text | PDF Plant biology: Blocking galactolipid biosynthesis pp761 - 762 Kent D Chapman doi:10.1038/nchembio.691 The first selective inhibitor of monogalactosyldiacylglycerol (MGDG) synthase was identified from a chemical library screen. The competitive inhibitor effectively targets MGDG concentrations across plant tissues and was used to demonstrate a new role for galactolipids in pollen-tube development. Full Text | PDF See also: Article by Botté et al. Chemical Biology JOBS of the week Postdoctoral or PhD position available: Ice-sheet modelling and coupling to mass-balance models, University of Lapland, Finland Arctic Centre, University of Lapland Rovaniemi, FI Regulatory Affairs Process Manager - CRO Paramount Recruitment Buckingham, US High-throughput screening bioinformatician The Institute for Molecular Medicine Finland (FIMM) Helsinki, FI Bioinformatician for the analysis of next generation sequencing data The Institute for Molecular Medicine Finland (FIMM) Helsinki, FI Business Representative Beijing Genomics Institute-Europe A/S DK More Science jobs from Chemical Biology EVENT Proteomics, Interactomes (F2) 7-12 May, 2012 Stockholm, Sweden More science events from Brief Communications Top Metabolomics annotates ABHD3 as a physiologic regulator of medium-chain phospholipids pp763 - 765 Jonathan Z Long, Justin S Cisar, David Milliken, Sherry Niessen, Chu Wang, Sunia A Trauger, Gary Siuzdak and Benjamin F Cravatt doi:10.1038/nchembio.659 An untargeted metabolomics approach identifies C14 phosphatidylcholines (PCs) as specific cellular medium-chain substrates of the lipase ABHD3, as well as C5–C8 short-chain PCs including oxidized pro-atherosclerotic and pro-apoptotic PC phospholipids. First paragraph | Full Text | PDF | Chemical compounds Structural basis for cytokinin recognition by Arabidopsis thaliana histidine kinase 4  pp766 - 768 Michael Hothorn, Tsegaye Dabi and Joanne Chory doi:10.1038/nchembio.667 Histidine kinase 4 from Arabidopsis thaliana (AHK4) is a membrane-bound receptor for cytokinins, a class of plant hormones involved in growth, development and defense. Crystal structures of the AHK4 sensor domain in complex with various natural and synthetic cytokinins reveal important features of ligand recognition by this cytokinin receptor. First paragraph | Full Text | PDF Articles Top Ligand discovery from a dopamine D3 receptor homology model and crystal structure pp769 - 778 Jens Carlsson, Ryan G Coleman, Vincent Setola, John J Irwin, Hao Fan, Avner Schlessinger, Andrej Sali, Bryan L Roth and Brian K Shoichet doi:10.1038/nchembio.662 A virtual screen of the GPCR D3R based on a homology model prior to publication of the crystal structure and a subsequent virtual screen based on the crystal structure of the receptor once it became available both identified new ligands with verified activities. Abstract | Full Text | PDF | Chemical compounds RF1 knockout allows ribosomal incorporation of unnatural amino acids at multiple sites pp779 - 786 David B F Johnson, Jianfeng Xu, Zhouxin Shen, Jeffrey K Takimoto, Matthew D Schultz, Robert J Schmitz, Zheng Xiang, Joseph R Ecker, Steven P Briggs and Lei Wang doi:10.1038/nchembio.657 Nonsense suppression, or reassigning stop codons to encode for other amino acids, offers a method for expanding the genetic code of proteins. Deletion of release factor 1 in an Escherichia coli strain enables the incorporation of non-natural amino acids into proteins at multiple sites. Abstract | Full Text | PDF A chemical-genetic screen reveals a mechanism of resistance to PI3K inhibitors in cancer pp787 - 793 Markus K Muellner, Iris Z Uras, Bianca V Gapp, Claudia Kerzendorfer, Michal Smida, Hannelore Lechtermann, Nils Craig-Mueller, Jacques Colinge, Gerhard Duernberger and Sebastian M B Nijman doi:10.1038/nchembio.695 A chemical-genetic study predicts mechanisms of resistance to PI3K inhibitors. Activation of NOTCH signaling, which leads to c-MYC expression, can overcome cancer cell dependency on PI3K signaling for growth. NOTCH and PI3K have not previously been linked in breast cancer. Abstract | Full Text | PDF A mass spectrometry–guided genome mining approach for natural product peptidogenomics pp794 - 802 Roland D Kersten, Yu-Liang Yang, Yuquan Xu, Peter Cimermancic, Sang-Jip Nam, William Fenical, Michael A Fischbach, Bradley S Moore and Pieter C Dorrestein doi:10.1038/nchembio.684 Peptidic natural products are theoretically amenable to characterization by mass spectrometry, but proteomics programs are not trained to discover these compounds. A new strategy uses mass spectrometry and bioinformatics iteratively to rapidly identify both ribosomal and nonribosomal sequences, yielding multiple new compounds. Abstract | Full Text | PDF (R)-Profens are substrate-selective inhibitors of endocannabinoid oxygenation by COX-2  pp803 - 809 Kelsey C Duggan, Daniel J Hermanson, Joel Musee, Jeffery J Prusakiewicz, Jami L Scheib, Bruce D Carter, Surajit Banerjee, J A Oates and Lawrence J Marnett doi:10.1038/nchembio.663 Rapid reversible inhibitors of the oxygenation activity of COX-2, including ibuprofen and naproxen, selectively inhibit the enzyme with endocannabinoid 2-AG substrates but not with arachidonic acid, and this substrate-selective inhibition may be important for the analgesic activity of the drugs. Abstract | Full Text | PDF On-resin N-methylation of cyclic peptides for discovery of orally bioavailable scaffolds pp810 - 817 Tina R White, Chad M Renzelman, Arthur C Rand, Taha Rezai, Cayla M McEwen, Vladimir M Gelev, Rushia A Turner, Roger G Linington, Siegfried S F Leung, Amit S Kalgutkar, Jonathan N Bauman, Yizhong Zhang, Spiros Liras, David A Price, Alan M Mathiowetz, Matthew P Jacobson and R Scott Lokey doi:10.1038/nchembio.664 A single trimethylated species is obtained in an on-resin N-methylation reaction of a cyclic hexapeptide. This regioselectivity is driven by conformation and the presence of intramolecular hydrogen bonds, and is correlated with membrane permeability of the peptides. Abstract | Full Text | PDF | Chemical compounds Affinity-based proteomics reveal cancer-specific networks coordinated by Hsp90 pp818 - 826 Kamalika Moulick, James H Ahn, Hongliang Zong, Anna Rodina, Leandro Cerchietti, Erica M Gomes DaGama, Eloisi Caldas-Lopes, Kristin Beebe, Fabiana Perna, Katerina Hatzi, Ly P Vu, Xinyang Zhao, Danuta Zatorska, Tony Taldone, Peter Smith-Jones, Mary Alpaugh, Steven S Gross, Nagavarakishore Pillarsetty, Thomas Ku, Jason S Lewis, Steven M Larson, Ross Levine, Hediye Erdjument-Bromage, Monica L Guzman, Stephen D Nimer, Ari Melnick, Len Neckers and Gabriela Chiosis doi:10.1038/nchembio.670 The inhibitor PU-H71 preferentially targets tumor-enriched Hsp90 complexes. Affinity purification using PU-H71 reveals cancer-specific protein networks in chronic myeloid leukemia and that the abundance of tumor-specific Hsp90 clients in cells can predict sensitivity to Hsp90 inhibitors. Abstract | Full Text | PDF The proteoglycan bikunin has a defined sequence pp827 - 833 Mellisa Ly, Franklin E Leach III, Tatiana N Laremore, Toshihiko Toida, I Jonathan Amster and Robert J Linhardt doi:10.1038/nchembio.673 Complex polysaccharides are generally thought not to have a defined carbohydrate sequence because their synthesis is not template-directed. Detailed mass spectrometry of bikunin now counters this dogma, showing that each molecular weight species consists of only a single sequence. Abstract | Full Text | PDF See also: News and Views by Jones & Larive Chemical inhibitors of monogalactosyldiacylglycerol synthases in Arabidopsis thaliana  pp834 - 842 Cyrille Y Botté, Michael Deligny, Aymeric Roccia, Anne-Laure Bonneau, Nadia Saïdani, Hélène Hardré, Samia Aci, Yoshiki Yamaryo-Botté, Juliette Jouhet, Emmanuelle Dubots, Karen Loizeau, Olivier Bastien, Laurent Bréhélin, Jacques Joyard, Jean-Christophe Cintrat, Denis Falconet, Maryse A Block, Bernard Rousseau, Roman Lopez and Eric Maréchal doi:10.1038/nchembio.658 Mono- and digalactosyldiacylglycerols (MGDGs and DGDGs) are glycolipids that are central to plant metabolism and photosynthetic membrane biogenesis. Galvestine-1, a small molecule inhibitor of MGDG synthases that was identified in a high-throughput chemical screen in Arabidopsis thaliana, reveals a new role for these galactolipids in pollen-tube development. Abstract | Full Text | PDF | Chemical compounds See also: News and Views by Chapman Discovery of parallel pathways of kanamycin biosynthesis allows antibiotic manipulation pp843 - 852 Je Won Park, Sung Ryeol Park, Keshav Kumar Nepal, Ah Reum Han, Yeon Hee Ban, Young Ji Yoo, Eun Ji Kim, Eui Min Kim, Dooil Kim, Jae Kyung Sohng and Yeo Joon Yoon doi:10.1038/nchembio.671 Investigations into kanamycin biosynthesis and identification of new pathway intermediates surprisingly point to the substrate specificity of two glycosyltransferases as controlling flux into parallel pathways, allowing changes to product profiles and structures by varying these gatekeeper enzymes. Abstract | Full Text | PDF | Chemical compounds Corrigendum Top A TR(i)P in the air p853 Peter Zygmunt doi:10.1038/nchembio1111-853 Full Text | PDF Top Advertisement Scientific American monthly table of contents e-alerts Sign up today! 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