Nature Chemical Biology Contents: December 2014 Volume 10 No 12 pp 984 - 1074

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TABLE OF CONTENTS December 2014 Volume 10, Issue 12 Research Highlights News and Views Review Brief Communications Articles Errata Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Announcing the Nature Index: A global indicator of high-quality research The Nature Index tracks the affiliations of high-quality scientific articles. Updated monthly, the Nature Index presents research outputs by institution and country. Use the Nature Index to interrogate publication patterns and to benchmark research performance.  Access the Nature Index free online.     Research Highlights Top Cell death: Jamming the switch | Cell walls: Cellulose snakes along | Transporters: A metal movement disorder | Drug discovery: Minimalist synthesis | Tools: A nice complement | Epigenetics: Bumping into BET inhibitors | Microbiomes: Gut persuasions | Target validation: Bringing the heat News and Views Top Metals: Setting a trap for copper   pp986 - 987 Valeria Culotta doi:10.1038/nchembio.1686 In the assembly of metalloenzymes, the matching of metals and proteins must occur with absolute precision. When zinc-starved, Chlamydomonas maintains its balance of metals by sequestering copper in electron-dense traps for metals, thus preventing mishaps in protein metallation. See also: Article by Hong-Hermesdorf et al. Protein dynamics: Tuning disorder propensity in p53   pp987 - 988 Richard W Kriwacki doi:10.1038/nchembio.1692 The dynamic interplay between p53 and Mdm2 triggers cell cycle arrest after DNA damage. A new study reveals that disorder in the transactivation domain of p53 is important for tuning this negative feedback system to ensure normal cellular signaling responses. See also: Brief Communication by Borcherds et al. Neuroinflammation: Modulating mighty microglia   pp988 - 989 Michelle L Block doi:10.1038/nchembio.1691 The small molecule inflachromene was discovered as a microglia-selective inhibitor of the central nervous system proinflammatory response and found to target HMGB2 and HMGB1 to impair proinflammatory signaling in microglia, resulting in neuroprotection. See also: Article by Lee et al. Chemical Biology JOBS of the week Faculty Positions Available at the State Key Laboratory of Medicinal Chemical Biology (Nankai University) Nankai University PhD Studentship in NMR Spectroscopy and Chemical Biology University of Auckland Postdoctoral Research Associate University of Wisconsin School of Medicine and Public Health Postdoctoral position in Single-Cell Biology of the Nucleus Karolinska Institutet (KI) Tier 2 Canada Research Chair in Systems Biology University of Ottawa More Science jobs from Chemical Biology EVENT Advances & Progress in Drug Design 16 February 2015 London, UK More science events from Review Top Recent strategies targeting HIV glycans in vaccine design   pp990 - 999 Satoru Horiya, Iain S MacPherson and Isaac J Krauss doi:10.1038/nchembio.1685 Carbohydrate antigens on HIV are important for viral biology as well as for recognition by glycan-reactive broadly neutralizing antibodies such as 2G12. A review of recent strategies targeting HIV glycans discusses the characterization and manipulation of glycopeptide epitopes for use as potential vaccines. Brief Communications Top Disorder and residual helicity alter p53-Mdm2 binding affinity and signaling in cells   pp1000 - 1002 Wade Borcherds, François-Xavier Theillet, Andrea Katzer, Ana Finzel, Katie M Mishall et al. doi:10.1038/nchembio.1668 Increasing residual helicity in the p53 transcriptional activation domain strengthened interactions with Mdm2, resulting in alterations in p53 protein dynamics, impaired transcription of target genes and failure to promote cell cycle arrest. See also: News and Views by Kriwacki Diels-Alder reaction–triggered bioorthogonal protein decaging in living cells   pp1003 - 1005 Jie Li, Shang Jia and Peng R Chen doi:10.1038/nchembio.1656 Diels-Alder chemistry is widely used for bioconjugations, and one variant of the reaction can ‘deprotect’ a small molecule via spontaneous elimination. This activation chemistry is now demonstrated on biomolecules in cells at high yields in 10 minutes. Chemical compounds Articles Top Pharmacological targeting of the pseudokinase Her3   pp1006 - 1012 Ting Xie, Sang Min Lim, Kenneth D Westover, Michael E Dodge, Dalia Ercan et al. doi:10.1038/nchembio.1658 The use of ATP competitive kinase inhibitors against the pseudokinase Her3 has been largely unsuccessful. Hydrophobic tagging of a covalent kinase inhibitor promotes Her3 degradation and prevents productive dimerization and signaling. Chemical compounds A highly potent and selective Vps34 inhibitor alters vesicle trafficking and autophagy   pp1013 - 1019 Baptiste Ronan, Odile Flamand, Lionel Vescovi, Christine Dureuil, Laurence Durand et al. doi:10.1038/nchembio.1681 A small-molecule inhibitor of the type III phosphatidylinositol 3-kinase, Vps34, binds the ATP binding pocket and prevents vesicle trafficking and autophagy. Chemical compounds Digital switching in a biosensor circuit via programmable timing of gene availability   pp1020 - 1027 Nicolas Lapique and Yaakov Benenson doi:10.1038/nchembio.1680 A new synthetic biology circuit using recombinases to control the timing of downstream steps allows 1,000-fold differences in signal between on and off states, facilitating cell identification and selective turn-on of cytotoxic agents. Rice cytochrome P450 MAX1 homologs catalyze distinct steps in strigolactone biosynthesis   pp1028 - 1033 Yanxia Zhang, Aalt D J van Dijk, Adrian Scaffidi, Gavin R Flematti, Manuel Hofmann et al. doi:10.1038/nchembio.1660 Biosynthesis of the strigolactones—important plant hormones—has been solved up to carlactone. Biochemical and genetic evidence now demonstrate that homologous enzymes perform two subsequent oxidations, setting the strigolactone scaffold in place. Subcellular metal imaging identifies dynamic sites of Cu accumulation in Chlamydomonas   pp1034 - 1042 Anne Hong-Hermesdorf, Marcus Miethke, Sean D Gallaher, Janette Kropat, Sheel C Dodani et al. doi:10.1038/nchembio.1662 A collection of chemical tools and spectroscopic techniques demonstrate that Zn availability influences Cu+ storage and localization in the green alga Chlamydomonas, with Zn limitation causing the accumulation of Cu+ in lysosome-related organelles. Chemical compounds See also: News and Views by Culotta Hydrolysis of 2′3′-cGAMP by ENPP1 and design of nonhydrolyzable analogs   pp1043 - 1048 Lingyin Li, Qian Yin, Pia Kuss, Zoltan Maliga, José L Millán et al. doi:10.1038/nchembio.1661 By biochemical purification and functional validation using knockout animals, ENPP1 is now defined as a major hydrolase for 2′,3′-cGAMP, a cyclic dinucleotide generated during antiviral innate immunity. New nonhydrolyzable 2′,3′-cGAMP analogs are potent activators of this system. Chemical compounds Electrophilic activity-based RNA probes reveal a self-alkylating RNA for RNA labeling   pp1049 - 1054 Richard I McDonald, John P Guilinger, Shankar Mukherji, Edward A Curtis, Won I Lee et al. doi:10.1038/nchembio.1655 Activity-based probes (ABPs) are widely used for system-wide profiling of enzymatic activity. Electrophilic ABPs applied to genomic RNA libraries led to the isolation of a 42-nt RNA motif that was adapted as an alkylation-based RNA labeling strategy. Chemical compounds A small molecule binding HMGB1 and HMGB2 inhibits microglia-mediated neuroinflammation   pp1055 - 1060 Sanghee Lee, Youngpyo Nam, Ja Young Koo, Donghyun Lim, Jongmin Park et al. doi:10.1038/nchembio.1669 A screen for inhibitors of microglial activation of neuroinflammation identified the compound ICM, which is anti-inflammatory and neuroprotective by targeting HMGB1 and HMGB2, implicating these proteins in a toxic microglial response. Chemical compounds See also: News and Views by Block Spatial encoding of cyclic AMP signaling specificity by GPCR endocytosis   pp1061 - 1065 Nikoleta G Tsvetanova and Mark von Zastrow doi:10.1038/nchembio.1665 β2-adrenergic receptor–mediated cAMP signaling from internal compartments is more effective compared to the plasma membrane in regulating a distinct set of genes, demonstrating a functional significance for the spatial separation of cAMP signaling. Covalent docking of large libraries for the discovery of chemical probes   pp1066 - 1072 Nir London, Rand M Miller, Shyam Krishnan, Kenji Uchida, John J Irwin et al. doi:10.1038/nchembio.1666 A modification of the in silico screening tool, DOCK, allows for identification of compounds that covalently modify catalytic and noncatalytic protein nucleophiles to modulate the activities of bacterial β-lactamase and the kinases RSK2, MSK1 and JAK3. Chemical compounds Errata Top Erratum: Bases of DNA repair and regulation   p1074 Adam B Robertson, John Arne Dahl and Arne Klungland doi:10.1038/nchembio1214-1074a Erratum: Notch inhibition allows oncogene-independent generation of iPS cells   p1074 Justin K Ichida, Julia T C W, Luis A Williams, Ava C Carter, Yingxiao Shi et al. doi:10.1038/nchembio1214-1074b Erratum: Notch inhibition allows oncogene-independent generation of iPS cells   p1074 Justin K Ichida, Julia T C W, Luis A Williams, Ava C Carter, Yingxiao Shi et al. doi:10.1038/nchembio1214-1074c Top Advertisement Nature Outlook: Medical Research Masterclass From the basic functions of the cell to cures for HIV and cancer, Nature Outlook: Medical Research Masterclass uses the 2014 Lindau Nobel Laureate Meeting as a basis to explore the latest research in medicine and physiology. Access the Outlook free online for six months.  Supported by Mars, Incorporated   Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. 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