Nature Chemical Biology Contents: January 2012 Volume 8 Number 1, pp 1 - 132

TABLE OF CONTENTS January 2012 Volume 8, Issue 1 Focus Editorial Commentaries Research Highlights News and Views Perspective Reviews Articles Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nature Chemical Biology Focus on Microbiology This Focus features a collection of articles aimed at understanding the chemical interactions of microbes with their environment, with an aim towards new anti-microbials and new biological insights. Access this special Focus today by visiting: www.nature.com/nchembio/focus/microbiology/index.html   Focus Top Microbiology Small molecules play important roles as metabolites in the physiology, ecology and evolution of microorganisms. This issue includes a collection of articles aimed at understanding the chemical interactions of microbes with their environment, with an aim towards new anti-microbials and new biological insights. Microbiology Editorial Top Talking microbes p1 doi:10.1038/nchembio.762 Understanding the molecules and mechanisms that microbes use to interact with each other and their environments can lead to better antimicrobial drug design as well as a richer understanding of bacterial physiology, ecology and evolution. Full Text | PDF Commentaries Top What counters antibiotic resistance in nature? pp2 - 5 Remy Chait, Kalin Vetsigian and Roy Kishony doi:10.1038/nchembio.745 Antibiotics promote the spread of resistance in the clinic, but various mechanisms may exist in natural environments that tilt the balance toward antibiotic sensitivity. Studying such mechanisms could help us understand the evolutionary dynamics of resistance and sensitivity in the wild, which may inspire new therapeutic strategies. Full Text | PDF Microbial environments confound antibiotic efficacy pp6 - 9 Henry H Lee and James J Collins doi:10.1038/nchembio.740 Despite our continued efforts to assert control over pathogens, more and more bacteria are saying "no" to drugs. It is becoming increasingly apparent that microbial environments, influenced by intracellular and extracellular metabolic processes, modulate antibiotic susceptibility in bacteria. A deeper understanding of these environmental processes may prove crucial for the development of new antibacterial therapies. Full Text | PDF Sociomicrobiology in engineered landscapes pp10 - 13 Jodi L Connell, Marvin Whiteley and Jason B Shear doi:10.1038/nchembio.749 A growing body of evidence points to the importance of microcolonies in the dissemination of bacteria, yet there is a dearth of tools for systematically assessing the behavior of cells within such communities. New strategies for landscaping three-dimensional culture environments on microscopic scales may have a critical role in revealing how bacteria orchestrate antibiotic resistance and other social behaviors within small, dense aggregates. Full Text | PDF Bacterial outer membrane evolution via sporulation? pp14 - 18 Waldemar Vollmer doi:10.1038/nchembio.748 The distinction between different cell-envelope architectures has defined much of our thinking about bacterial systematics, but the evolution of different envelope layers has been harder to understand. A recent publication focused on the non-model organism Acetonema longum provides important clues to the possible origin of the second membrane typical of Gram-negative bacteria. Full Text | PDF Research Highlights Top Host-microbial interactions: F-box for energy | Metabolism: A Warburg shakeup | Neuronal function: A Doc uses calcium | Biosynthesis: Sacrificial sulfur | Drug discovery: Malaria under arrest | Synthetic biology: Cellular xDNA readers | Cancer: KEAPing NRF in check | Microbial ecology: When things go bad News and Views Top Lipids: LPA activates TRPV1—and it hurts pp22 - 23 Gabor Tigyi doi:10.1038/nchembio.738 Lysophosphatidic acid, a lipid mediator, second messenger and intermediate in lipid biosynthesis, finds a new intracellular target in TRPV1. This nonselective cation channel is also targeted by the analgesic capsaicin, which acts to desensitize the channel. Full Text | PDF See also: Article by Nieto-Posadas et al. Metabolism: Amino acid regulatory wisdom pp23 - 24 Tamar Avin-Wittenberg and Gad Galili doi:10.1038/nchembio.743 Amino acids not only are useful for protein synthesis but also act as regulators of gene expression. An elegant genome-wide approach now shows how binding of amino acids to transcription factors regulates an integrated network of amino acid metabolism to suit the physiological needs of bacterial cells. Full Text | PDF See also: Article by Cho et al. Nuclear replication: Hidden iron-sulfur clusters pp24 - 25 Scott Bailey doi:10.1038/nchembio.737 The multisubunit DNA polymerases of eukaryotes have iron-sulfur centers that are crucial for polymerase assembly and therefore the integrity of the nuclear genome. Full Text | PDF See also: Article by Netz et al. Chemical Biology JOBS of the week Chair in Medicinal Chemistry University of London Bioanalytical Chemist / Biochemist Celloxess LLC, Ph.D. student in Chemical Carcinogenesis (pharmacology / biochemistry / biology) Dept of Immunology, Centre de Recherche Public de la Santé, National Public Health Institute Tenure-Track Positions The University of Texas Cell Culture Technician Kelly Scientific Resources More Science jobs from Chemical Biology EVENT Therapeutic Applications of Computational Biology and Chemistry (TACBAC) 2012 12-14 March, 2012 Cambridge, UK More science events from Perspective Top Microbial metabolic exchange—the chemotype-to-phenotype link pp26 - 35 Vanessa V Phelan, Wei-Ting Liu, Kit Pogliano and Pieter C Dorrestein doi:10.1038/nchembio.739 Abstract | Full Text | PDF Reviews Top Bacteria and host interactions in the gut epithelial barrier pp36 - 45 Hiroshi Ashida, Michinaga Ogawa, Minsoo Kim, Hitomi Mimuro and Chihiro Sasakawa doi:10.1038/nchembio.741 Abstract | Full Text | PDF Bugs, drugs and chemical genomics pp46 - 56 Terry Roemer, Julian Davies, Guri Giaever and Corey Nislow doi:10.1038/nchembio.744 Abstract | Full Text | PDF Articles Top Peroxide-dependent sulfenylation of the EGFR catalytic site enhances kinase activity pp57 - 64 Candice E Paulsen, Thu H Truong, Francisco J Garcia, Arne Homann, Vinayak Gupta, Stephen E Leonard and Kate S Carroll doi:10.1038/nchembio.736 A sensitive probe that detects protein sulfenylation in cells reveals that sulfenylation of the active site cysteine in EGFR enhances its kinase activity. Abstract | Full Text | PDF | Chemical compounds Deciphering the transcriptional regulatory logic of amino acid metabolism pp65 - 71 Byung-Kwan Cho, Stephen Federowicz, Young-Seoub Park, Karsten Zengler and Bernhard Ø Palsson doi:10.1038/nchembio.710 Genome-scale metabolic models provide a map of biochemical reactions in the cell but do not indicate how these reactions are regulated by complex transcriptional networks. Analysis of expression and interaction data now define two distinct roles for amino acids as signaling and nutrient molecules. Abstract | Full Text | PDF See also: News and Views by Avin-Wittenberg & Galili A neutral diphosphate mimic crosslinks the active site of human O-GlcNAc transferase  pp72 - 77 Jiaoyang Jiang, Michael B Lazarus, Lincoln Pasquina, Piotr Sliz and Suzanne Walker doi:10.1038/nchembio.711 The mass spectrometry and crystallographic characterization of an irreversible O-glycosyltransferase inhibitor surprisingly indicates that the dicarbamate core reacts to form an unusual carbonyl crosslink between two active site residues, probably driven by its ability to serve as a diphosphate mimic. Abstract | Full Text | PDF | Chemical compounds Lysophosphatidic acid directly activates TRPV1 through a C-terminal binding site pp78 - 85 Andrés Nieto-Posadas, Giovanni Picazo-Juárez, Itzel Llorente, Andrés Jara-Oseguera, Sara Morales-Lázaro, Diana Escalante-Alcalde, León D Islas and Tamara Rosenbaum doi:10.1038/nchembio.712 Lysophosphatidic acid (LPA), a lipid that induces neuropathic pain, functions by binding directly to the ion channel TRPV1 independently from the G protein–coupled receptors that generally mediate LPA function. Abstract | Full Text | PDF See also: News and Views by Tigyi Mechanical modulation of catalytic power on F1-ATPase pp86 - 92 Rikiya Watanabe, Daichi Okuno, Shouichi Sakakihara, Katsuya Shimabukuro, Ryota Iino, Masasuke Yoshida and Hiroyuki Noji doi:10.1038/nchembio.715 Single-molecule studies on a molecular motor F1-ATPase provide evidence that energy from catalysis is gradually converted to mechanical rotation, explaining the high efficiency of energy conversion and the mechanism for positive cooperativity among subunits during ATP hydrolysis. Abstract | Full Text | PDF Small-molecule conversion of toxic oligomers to nontoxic β-sheet–rich amyloid fibrils pp93 - 101 Jan Bieschke, Martin Herbst, Thomas Wiglenda, Ralf P Friedrich, Annett Boeddrich, Franziska Schiele, Daniela Kleckers, Juan Miguel Lopez del Amo, Björn A Grüning, Qinwen Wang, Michael R Schmidt, Rudi Lurz, Roger Anwyl, Sigrid Schnoegl, Marcus Fändrich, Ronald F Frank, Bernd Reif, Stefan Günther, Dominic M Walsh and Erich E Wanker doi:10.1038/nchembio.719 An orcein-related small molecule can drive polymerization of amyloid-β, implicated in Alzheimer's disease, without remodeling oligomeric or fibril forms but by stabilizing a seeding-competent protofilament state and shortening the lag phase of spontaneous polymerization. Abstract | Full Text | PDF FERM domain interaction with myosin negatively regulates FAK in cardiomyocyte hypertrophy pp102 - 110 Aline M Santos, Deborah Schechtman, Alisson C Cardoso, Carolina F M Z Clemente, Júlio C Silva, Mariana Fioramonte, Michelle B M Pereira, Talita M Marin, Paulo S L Oliveira, Ana Carolina M Figueira, Saulo H P Oliveira, Íris L Torriani, Fábio C Gozzo, José Xavier Neto and Kleber G Franchini doi:10.1038/nchembio.717 An intramolecular cleft of the FAK FERM domain mediates interaction with sarcomeric myosin. Chemical cross-linking, SAXS and mutational analyses confirm the interaction, and inhibiting the interaction with a peptide activates FAK and promotes the cardiomyocyte hypertrophic response. Abstract | Full Text | PDF Structural basis for an inositol pyrophosphate kinase surmounting phosphate crowding pp111 - 116 Huanchen Wang, J R Falck, Traci M Tanaka Hall and Stephen B Shears doi:10.1038/nchembio.733 Enzymes that act on inositol pyrophosphates must accommodate a densely charged substrate while retaining excellent substrate specificity to control downstream signaling networks. Structural and biochemical data now define the basis for substrate recognition and the reaction coordinate for formation of a high-energy pyrophosphate bond. Abstract | Full Text | PDF Unusual carbon fixation gives rise to diverse polyketide extender units pp117 - 124 Nick Quade, Liujie Huo, Shwan Rachid, Dirk W Heinz and Rolf Müller doi:10.1038/nchembio.734 Biochemical and bioinformatic analyses have pointed to crotonyl-CoA carboxylase-reductase homolog as responsible for introducing unusual extender units into polyketide pathways; structural and mutational analysis now defines the basis for this reaction and the mechanism for substrate discrimination. Abstract | Full Text | PDF Eukaryotic DNA polymerases require an iron-sulfur cluster for the formation of active complexes pp125 - 132 Daili J A Netz, Carrie M Stith, Martin Stümpfig, Gabriele Köpf, Daniel Vogel, Heide M Genau, Joseph L Stodola, Roland Lill, Peter M J Burgers and Antonio J Pierik doi:10.1038/nchembio.721 DNA polymerases contain two cysteine-rich metal binding motifs (CysA and CysB), which have been assigned as zinc-ion binding sites by structural studies. A combination of biochemical and spectroscopic techniques reveal that the CysB site of yeast B-family polymerases binds a [4Fe-4S] cluster that is essential for polymerase function. Abstract | Full Text | PDF See also: News and Views by Bailey Top Advertisement Nature.com presents Antibodypedia Finding the right antibody for the right application just got easier! Visit www.antibodypedia.com to find antibodies that have proved themselves effective for particular applications or to submit antibody validation data from your own experiments.   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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