TABLE OF CONTENTS | August 2012 Volume 8, Issue 8 |  |  |  |  | Editorial Commentaries Research Highlights News and Views Review Brief Communications Articles Corrigenda Errata
| |  | |  | Advertisement |  | |  | | | | Advertisement |  | Nature Chemical Biology Focus on Metabolism in 3D In this focus issue, we feature a collection of commentary and review articles that outline some of the ideas, advances and goals that are laying the foundations for the next era of metabolism research. To access the Focus, visit: http://www.nature.com/nchembio/focus/metabolism3d/index.html | |  | | | Editorial | Top |  |  |  | Raising the bar p669 doi:10.1038/nchembio.1039 We are changing the way we evaluate papers to ensure timely dissemination of chemical biology research.
|  | Commentaries | Top |  |  |  | A new era of GPCR structural and chemical biology pp670 - 673 Sebastien Granier and Brian Kobilka doi:10.1038/nchembio.1025 G protein-coupled receptors (GPCRs) are versatile molecular machines that regulate the majority of physiological responses to chemically diverse hormones and neurotransmitters. Recent breakthroughs in structural studies have advanced our understanding of GPCR signaling, particularly the selectivity of ligand recognition and receptor activation of G proteins.
|  |  |  | Where have all the active receptor states gone? pp674 - 677 H Ongun Onaran and Tommaso Costa doi:10.1038/nchembio.1024 Defining G protein-coupled receptor ligand efficacy and biased agonism in precise chemical terms is one challenge posed by the current structural data that exists for this receptor family. Concepts classically used for understanding enzymes and other nonreceptor proteins may lead us in the right direction.
|  | Research Highlights | Top |  |  |  | Methods: How to get GAT | Cell cycle: The double life of IMPDH | Synthesis: Cyclobutanes prove charlatans | Metabolic disorders: Lipids go deaf | Epigenetics: Programming chromatin | Signaling: In Wnt's grasp | Drug discovery: Polypharmacology on the fly | RNA: Hitting translation first | News and Views | Top |  |  |  | |  | Review | Top |  |  |  | Developing inhibitors of glycan processing enzymes as tools for enabling glycobiology pp683 - 694 Tracey M Gloster and David J Vocadlo doi:10.1038/nchembio.1029

Dissecting the often subtle or time-sensitive roles of glycans in biology demands an increased availability of high-quality inhibitors for carbohydrate-processing enzymes. A review of lessons learned from other fields and considerations unique to glycobiology provides guidelines for development of these critical chemical tools.
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|  | Brief Communications | Top |  |  |  | Lys34 of translation elongation factor EF-P is hydroxylated by YfcM pp695 - 697 Lauri Peil, Agata L Starosta, Kai Virumäe, Gemma C Atkinson, Tanel Tenson, Jaanus Remme and Daniel N Wilson doi:10.1038/nchembio.1001

Elongation factor P is a conserved translational regulatory protein that has an unusual post-translational modification, in which Lys34 forms an amide linkage to (R)-β-lysine. Further characterization reveals that Lys34 is also hydroxylated, drawing parallels to a functional modification of eukaryotic initiation factor 5A.
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|  |  |  | Metallo-β-lactamases withstand low Zn(II) conditions by tuning metal-ligand interactions pp698 - 700 Javier M González, María-Rocío Meini, Pablo E Tomatis, Francisco J Medrano Martín, Julia A Cricco and Alejandro J Vila doi:10.1038/nchembio.1005

Bacterial resistance is propagated in part by metallo-β-lactamases, which hydrolyze and inactivate β-lactam antibiotics. An unusual cysteine residue in the active site is now shown to be critical for retaining the second metal ion, and thus enzyme activity, at low zinc concentrations.
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|  | Articles | Top |  |  |  | Phenylalanine assembly into toxic fibrils suggests amyloid etiology in phenylketonuria pp701 - 706 Lihi Adler-Abramovich, Lilach Vaks, Ohad Carny, Dorit Trudler, Andrea Magno, Amedeo Caflisch, Dan Frenkel and Ehud Gazit doi:10.1038/nchembio.1002

Phenylketonuria (PKU) is characterized by increased levels of phenylalanine in the blood and progressive mental retardation. Now, phenylalanine is shown to form toxic amyloid fibrils at high concentrations, which accumulate in the brains of PKU patients and mouse models.
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|  |  |  | |  |  |  | Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration pp714 - 724 Motohiro Nishida, Tomohiro Sawa, Naoyuki Kitajima, Katsuhiko Ono, Hirofumi Inoue, Hideshi Ihara, Hozumi Motohashi, Masayuki Yamamoto, Makoto Suematsu, Hitoshi Kurose, Albert van der Vliet, Bruce A Freeman, Takahiro Shibata, Koji Uchida, Yoshito Kumagai and Takaaki Akaike doi:10.1038/nchembio.1018

Hydrogen sulfide anion reacts with cellular electrophiles, including 8-nitro-cGMP, and sulfhydration products inhibit S-guanylation–dependent H-Ras activation in cardiac inflammatory injury models.
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|  |  |  | Mechanism of N-terminal modulation of activity at the melanocortin-4 receptor GPCR pp725 - 730 Baran A Ersoy, Leonardo Pardo, Sumei Zhang, Darren A Thompson, Glenn Millhauser, Cedric Govaerts and Christian Vaisse doi:10.1038/nchembio.1008

Different key residues mediate melanocortin-4 receptor activation via the agonist αMSH or constitutive activation via interaction of the transmembrane domain with the N-terminal domain, and these modes are further distinguishable by the different effects of the physiological antagonist.
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|  |  |  | |  | Corrigenda | Top |  |  |  | A selective inhibitor reveals PI3Kγ dependence of TH17 cell differentiation p737 Giovanna Bergamini, Kathryn Bell, Satoko Shimamura, Thilo Werner, Andrew Cansfield, Katrin Muller, Jessica Perrin, Christina Rau, Katie Ellard, Carsten Hopf, Carola Doce, Daniel Leggate, Raffaella Mangano, Toby Mathieson, Alison O'Mahony, Ivan Plavec, Faiza Rharbaoui, Friedrich Reinhard, Mikhail M Savitski, Nigel Ramsden, Emilio Hirsch, Gerard Drewes, Oliver Rausch, Marcus Bantscheff and Gitte Neubauer doi:10.1038/nchembio0812-737b
|  |  |  | Lysophosphatidic acid directly activates TRPV1 through a C-terminal binding site p737 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/nchembio0812-737c
|  |  |  | A biosensor generated via high-throughput screening quantifies cell edge Src dynamics p737 Akash Gulyani, Eric Vitriol, Richard Allen, Jianrong Wu, Dmitriy Gremyachinskiy, Steven Lewis, Brian Dewar, Lee M Graves, Brian K Kay, Brian Kuhlman, Tim Elston and Klaus M Hahn doi:10.1038/nchembio0812-737d
|  | Errata | Top |  |  |  | The radical SAM enzyme AlbA catalyzes thioether bond formation in subtilosin A p737 Leif Flühe, Thomas A Knappe, Michael J Gattner, Antje Schäfer, Olaf Burghaus, Uwe Linne and Mohamed A Marahiel doi:10.1038/nchembio0812-737a
|  |  |  | Research Highlights p737 doi:10.1038/nchembio0812-737e
|  | Top |  |  | | Advertisement |  | Nature Structural & Molecular Biology FOCUS ON TRANSLATIONAL CONTROL Translational control has become a major focus of attention and research activity. The identification of a myriad of new factors and genome-wide targets as well as recent insights into eukaryotic ribosomes, translation initiation and control mechanisms will be discussed in four Reviews and one Perspective by leaders in the field. Access the Focus online: www.nature.com/nsmb/focus/translation | |  | | |  |  |  |  |  |  | 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 |  |  |  |  |  | |  | |
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