Nature Chemical Biology Contents: January 2014 Volume 10 Number 1 pp 2 - 84

TABLE OF CONTENTS January 2014 Volume 10, Issue 1 Research Highlights News and Views Review Brief Communication Articles Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement NatureJournals app for ipad The NatureJournals app for iPad now boasts over 25 Nature-branded titles. Subscribe to any journal in the app for $35.99* and gain access to world class research on the move. www.nature.com/content/app/anytitleoffer *Apple exchange rates apply. Limited time offer available on all journals except Scientific Reports. iPad is a trademark of Apple Inc.   Research Highlights Top Signaling: A Norrin trio | Neurodegeneration: Toward taming toxicity | Enzymes: I branches out | Ribozymes: Now for splicing! | Gas sensing: CO2 speaks for itself | Olfaction: Computational transformation | Natural products: Sweet dreams are made of this | Metabolic regulation: Glucose balancing act News and Views Top Metabolism: Digging up enzyme functions   pp4 - 5 Matthew J Wargo doi:10.1038/nchembio.1413 Advances in genome sequencing and structural biology mean that we are now buried under an avalanche of predicted domains and structures of proteins with unknown functions. Two groups have used different methods to unearth the functions of previously cryptic bacterial enzymes, illuminating new reactions and metabolic pathways. See also: Article by Bastard et al. Wnt acylation: Seeing is believing   pp5 - 7 Luc G Berthiaume doi:10.1038/nchembio.1414 A highly original and sensitive method using clickable bioorthogonal fatty acids and in situ proximity ligation enables the visualization of the palmitoylation of not only Wnt but also its fatty acyltransferase Porcupine in cells. See also: Article by Gao & Hannoush Immunology: Glyco-engineering 'super-self'   pp7 - 8 Matthew S Macauley and James C Paulson doi:10.1038/nchembio.1415 Altered glycosylation of cancer cells confers phenotypic changes that promote spread and evasion of immune responses. A new method for engineering cell surface glycans is providing insights into these mechanisms. See also: Article by Hudak et al. Chemical Biology JOBS of the week Tenure-Track Faculty Positions in Chemical Biology University of Utah Postdoctoral Associate in Molecular Biology University of Minnesota - Twin Cities Technical Assistant Virology (m / f) Boehringer Ingelheim 4 PhD student positions on 'Dynamics of coagulation Factor VIII, von Willebrand factor and endothelial cells' at Sanquin Research, Amsterdam, The Netherlands Sanquin Research Associate Scientist Sanford-Burnham Medical Research Institute More Science jobs from Chemical Biology EVENT Chemical Biology Discussion Group Year-End Symposium 3 June 2014 New York, USA More science events from Review Top The role of iron and reactive oxygen species in cell death   pp9 - 17 Scott J Dixon and Brent R Stockwell doi:10.1038/nchembio.1416 Iron is essential for biological systems but can also damage or kill cells, leading to a variety of disease states. A review of mechanisms leading to Fe- and ROS-dependent cell death highlights the vast array of open questions in this complex field. Brief Communication Top Dynamic ligand binding dictates partial agonism at a G protein–coupled receptor   pp18 - 20 Andreas Bock, Brian Chirinda, Fabian Krebs, Regina Messerer, Julia Bätz et al. doi:10.1038/nchembio.1384 Partial agonists are generally thought to promote GPCR conformations that signal suboptimally. Analysis of bifunctional muscarinic M2 receptor ligands now shows that partial agonism can also be predictably defined by a single ligand binding two receptor populations in different orientations. Chemical compounds Articles Top The multiple antibiotic resistance regulator MarR is a copper sensor in Escherichia coli   pp21 - 28 Ziyang Hao, Hubing Lou, Rongfeng Zhu, Jiuhe Zhu, Dianmu Zhang et al. doi:10.1038/nchembio.1380 Drugs and antibiotics induce oxidation and mobilization of membrane-bound copper(I) ions to copper(II) species within the E. coli cytosol, causing oxidation of a single cysteine residue of the multiple antibiotic-resistance regulator MarR, that leads to formation of disulfide-bonded MarR tetramers and release of dimers from sites of transcriptional activity. Chemical inhibition of prometastatic lysyl-tRNA synthetase–laminin receptor interaction   pp29 - 34 Dae Gyu Kim, Jin Young Lee, Nam Hoon Kwon, Pengfei Fang, Qian Zhang et al. doi:10.1038/nchembio.1381 Beyond its canonical role in translation, lysyl-tRNA synthetase (KRS) stabilizes the prometastatic 67-kDa laminin receptor (67LR) in the plasma membrane. A small-molecule inhibitor of the KRS-67LR interaction modulates the KRS-promoted metastatic potential of 67LR without disrupting the normal function of each protein. Chemical compounds Imperfect coordination chemistry facilitates metal ion release in the Psa permease   pp35 - 41 Rafael M Couñago, Miranda P Ween, Stephanie L Begg, Megha Bajaj, Johannes Zuegg et al. doi:10.1038/nchembio.1382 The PsaA binding protein delivers Mn2+ to the human pathogen Streptococcus pneumoniae. Structural and biochemical studies now explain its metal specificity, showing that metal binding induces a closed complex that is reversible for the desired substrate but irreversible for the inhibitor Zn2+. Revealing the hidden functional diversity of an enzyme family   pp42 - 49 Karine Bastard, Adam Alexander Thil Smith, Carine Vergne-Vaxelaire, Alain Perret, Anne Zaparucha et al. doi:10.1038/nchembio.1387 Enzyme annotations often suffer from incomplete functional information for homologous sequences. Extrapolation from one characterized enzyme to multiple possible substrate-enzyme pairs, using bioinformatics and experimental approaches, leads to four distinct β-keto acid cleavage enzyme functional motifs and assignment of 14 new activities. See also: News and Views by Wargo Direct evidence for a covalent ene adduct intermediate in NAD(P)H-dependent enzymes   pp50 - 55 Raoul G Rosenthal, Marc-Olivier Ebert, Patrick Kiefer, Dominik M Peter, Julia A Vorholt et al. doi:10.1038/nchembio.1385 NAD(P)H-dependent enzymes are generally assumed to use a one-step hydride transfer mechanism owing to a lack of evidence for alternative proposals. Spectrophotometric and NMR data now call this assumption into question, defining a covalent substrate-cofactor species that is catalytically competent in three unrelated enzymes. Chemical compounds A widespread self-cleaving ribozyme class is revealed by bioinformatics   pp56 - 60 Adam Roth, Zasha Weinberg, Andy G Y Chen, Peter B Kim, Tyler D Ames et al. doi:10.1038/nchembio.1386 To date, five classes of naturally occurring self-cleaving ribozymes have been reported. The bioinformatic discovery in bacteria and eukaryotes of twister RNAs, a new ribozyme class that contains a double pseudoknot fold, adds to the list of catalytic RNAs that have roles in cells. Single-cell imaging of Wnt palmitoylation by the acyltransferase porcupine   pp61 - 68 Xinxin Gao and Rami N Hannoush doi:10.1038/nchembio.1392 Clickable fatty acids coupled with in situ proximity ligation allow visualization of Wnt as it trafficks through the secretory pathway, defining roles for palmitoylation and glycosylation in controlling Wnt activity and exploring the substrate specificity and regulation of the Wnt-modifying porcupine. See also: News and Views by Berthiaume Glycocalyx engineering reveals a Siglec-based mechanism for NK cell immunoevasion   pp69 - 75 Jason E Hudak, Stephen M Canham and Carolyn R Bertozzi doi:10.1038/nchembio.1388 Defined phospholipid-functionalized glycopolymers serve as a new tool to identify the mechanistic connection between hypersialylation and immunoprotection, where hypersialylation of tumor cells subverts the immunosurveillance mechanism of NK cells by recruiting the lectin Siglec-7 to inhibit human NK cell activation. See also: News and Views by Macauley & Paulson PITPs as targets for selectively interfering with phosphoinositide signaling in cells   pp76 - 84 Aaron H Nile, Ashutosh Tripathi, Peihua Yuan, Carl J Mousley, Sundari Suresh et al. doi:10.1038/nchembio.1389 Phosphatidylinositol transfer proteins (PITPs) are important mediators of phosphoinositide signaling within cells. A small-molecule inhibitor of the PITP Sec14, identified by chemical screening and structure-based design, affects transit through the trans-Golgi network and endosomal system. Chemical compounds Top Advertisement Cell Research is a prestigious international journal in life sciences covering all areas related to molecular and cell biology. Impact Factor: 10.526* To view articles in the top ten articles downloads, please visit: www.nature.com/cr/topten *2012 Journal Citation Reports (Thomson Reuters, June 2013)   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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