Nature Chemical Biology Contents: November 2012 Volume 8 Number 11, pp 871 - 948

TABLE OF CONTENTS November 2012 Volume 8, Issue 11 Editorial Research Highlights News and Views Review Brief Communication Articles Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Nurture your career with the new-look Naturejobs As the world's largest dedicated jobs boards for the scientific community, Naturejobs is the ideal resource to build your career. Our new and improved functionality enables you to search, save and apply for jobs quickly and easily. Search over 10,000 vacancies to find exactly the right job for you at: www.naturejobs.com   Editorial Top Decoding ENCODE   p871 doi:10.1038/nchembio.1107 The ENCODE project provides fundamental insights into the genome and large-scale science, inspiring future collaboration at the genomics-chemical biology interface. Research Highlights Top Chaperones: Better with BACON | Synthetic biology: Genetic room to breathe | Neuroscience: Fixing fragility | Molecular biology: You can leave your cap on | Biosynthesis: Acting in self-defense | Receptor lipids: GM1 gets sorted | Proteasome inhibition: Missing amino acids | Biomaterials: In living color News and Views Top Protein engineering: A biocatalyst inspired by cancer   pp874 - 875 Lenny Dang doi:10.1038/nchembio.1090 A gain of function in the cancer-associated mutant of isocitrate dehydrogenase inspired protein engineering of Saccharomyces cerevisiae homoisocitrate dehydrogenase to create a 2-hydroxyadipate dehydrogenase. This neoactivity yields chirally pure (R)-2-hydroxyadipic acid, a synthetic precursor to the industrially valuable adipic acid used in pharmaceuticals and synthetic polymers. See also: Brief Communication by Reitman et al. Epigenetics: Stopping a chromatin enzyme   pp875 - 876 Jeffrey A Simon doi:10.1038/nchembio.1088 The first direct chemical inhibitor of a key histone-methylating enzyme provides a new tool to alter epigenetic states and genome expression profiles in normal and cancer cells. See also: Article by Knutson et al. Metabolism: Nothing to waste   pp877 - 878 Haruyuki Atomi doi:10.1038/nchembio.1089 A metabolic route including a RubisCO-like protein links polyamine metabolism with isoprenoid biosynthesis in the photosynthetic bacterium Rhodospirillum rubrum. Methanethiol is released in the pathway but is recaptured in the form of methionine, and thus methylthioadenosine, previously regarded as something of a byproduct of polyamine biosynthesis, is converted to two major cell components. See also: Article by Erb et al. Chemical Biology JOBS of the week Postdoctoral Researcher in Ecology and Evolutionary Biology University of Jyväskylä, Department of Biological and Environmental Science Professor in Translational Medicine and Director of Research Programs Unit University of Helsinki Professor Position Aalto University LiU Research Fellow - a minumum of four vacancies Linkoping University Neuroscience Postdoc Programmer Linkoping University More Science jobs from Chemical Biology EVENT World Forests Summit, Stockholm 5-6 March 2013 Stockholm, Sweden More science events from Review Top Force probing of individual molecules inside the living cell is now a reality   pp879 - 886 Lene B Oddershede doi:10.1038/nchembio.1082 Brief Communication Top Enzyme redesign guided by cancer-derived IDH1 mutations   pp887 - 889 Zachary J Reitman, Bryan D Choi, Ivan Spasojevic, Darell D Bigner, John H Sampson and Hai Yan doi:10.1038/nchembio.1065 A new approach for rational enzyme design uses gain-of-function cancer mutations to guide homologous mutations in homoisocitrate dehydrogenase, yielding a biocatalytic path to (R)-2-hydroxyadipate, a precursor for the major commodity chemical adipic acid. See also: News and Views by Dang Articles Top A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells   pp890 - 896 Sarah K Knutson, Tim J Wigle, Natalie M Warholic, Christopher J Sneeringer, Christina J Allain, Christine R Klaus, Joelle D Sacks, Alejandra Raimondi, Christina R Majer, Jeffrey Song, Margaret Porter Scott, Lei Jin, Jesse J Smith, Edward J Olhava, Richard Chesworth, Mikel P Moyer, Victoria M Richon, Robert A Copeland, Heike Keilhack, Roy M Pollock and Kevin W Kuntz doi:10.1038/nchembio.1084 EZH2 is a protein methyltransferase component of the polycomb repressive complex 2 (PRC2) that installs the H3K27me3 chromatin mark. EPZ005687 inhibits EZH2 function and H3K27 trimethylation in cells and selectively kills lymphoma cells that require EZH2 for proliferation. Chemical compounds See also: News and Views by Simon The orphan nuclear receptor Nur77 regulates LKB1 localization and activates AMPK   pp897 - 904 Yan-yan Zhan, Yan Chen, Qian Zhang, Jia-jia Zhuang, Min Tian, Hang-zi Chen, Lian-ru Zhang, Hong-kui Zhang, Jian-ping He, Wei-jia Wang, Rong Wu, Yuan Wang, Chunfang Shi, Kai Yang, An-zhong Li, Yong-zhen Xin, Terytty Yang Li, James Y Yang, Zhong-hui Zheng, Chun-dong Yu, Sheng-Cai Lin, Chawnshang Chang, Pei-qiang Huang, Tianwei Lin and Qiao Wu doi:10.1038/nchembio.1069 A small molecule that disrupts interaction between Nur77 and LKB1 leads to LKB1 exit from the nucleus to activate cytoplasmic AMPK and, ultimately, reduces blood glucose and insulin in diabetic mice. Chemical compounds Systems-pharmacology dissection of a drug synergy in imatinib-resistant CML   pp905 - 912 Georg E Winter, Uwe Rix, Scott M Carlson, Karoline V Gleixner, Florian Grebien, Manuela Gridling, André C Müller, Florian P Breitwieser, Martin Bilban, Jacques Colinge, Peter Valent, Keiryn L Bennett, Forest M White and Giulio Superti-Furga doi:10.1038/nchembio.1085 A systems-pharmacology approach reveals that the combined off-target activity of two kinase inhibitors that impedes MAPK signaling to decrease expression of Myc target genes increases apoptosis in CML cells containing gatekeeper mutations in BCR-ABL. Discovery and biological characterization of geranylated RNA in bacteria   pp913 - 919 Christoph E Dumelin, Yiyun Chen, Aaron M Leconte, Y Grace Chen and David R Liu doi:10.1038/nchembio.1070 Mass spectrometric profiling has revealed S-geranylation as a new tRNA modification and identified SelU as the tailoring enzyme in bacterial cells. Nucleotide S-geranylation was found in the anticodon of several tRNAs and regulates translational frameshifting and codon usage. Chemical compounds Discovery of an allosteric mechanism for the regulation of HCV NS3 protein function   pp920 - 925 Susanne M Saalau-Bethell, Andrew J Woodhead, Gianni Chessari, Maria G Carr, Joseph Coyle, Brent Graham, Steven D Hiscock, Christopher W Murray, Puja Pathuri, Sharna J Rich, Caroline J Richardson, Pamela A Williams and Harren Jhoti doi:10.1038/nchembio.1081 A compound derived from a structure-based screen binds to an allosteric site that includes residues of both the helicase and protease domains of HCV NS3, stabilizing an inactive conformation and inhibiting viral replication. Chemical compounds A RubisCO-like protein links SAM metabolism with isoprenoid biosynthesis   pp926 - 932 Tobias J Erb, Bradley S Evans, Kyuil Cho, Benjamin P Warlick, Jaya Sriram, B McKay Wood, Heidi J Imker, Jonathan V Sweedler, F Robert Tabita and John A Gerlt doi:10.1038/nchembio.1087 Combined omics techniques lead to the functional assignment of four enzymes involved in a new methionine salvage pathway linking polyamine metabolism with isoprenoid biosynthesis. This reaction sequence involves a homolog of nature's most abundant protein, the CO2-fixing enzyme RubisCO. See also: News and Views by Atomi An enzyme-trap approach allows isolation of intermediates in cobalamin biosynthesis   pp933 - 940 Evelyne Deery, Susanne Schroeder, Andrew D Lawrence, Samantha L Taylor, Arefeh Seyedarabi, Jitka Waterman, Keith S Wilson, David Brown, Michael A Geeves, Mark J Howard, Richard W Pickersgill and Martin J Warren doi:10.1038/nchembio.1086 The use of abbreviated pathway constructs leads to trapping of a series of cobalamin intermediates, allowing assignment of the full biosynthetic pathway and defining the roles of CobL as a dual-function methyltransferase and CobE as a likely carrier protein, perhaps facilitating metabolic channeling. Chemical compounds The catalytic center of ferritin regulates iron storage via Fe(II)-Fe(III) displacement   pp941 - 948 Kourosh Honarmand Ebrahimi, Eckhard Bill, Peter-Leon Hagedoorn and Wilfred R Hagen doi:10.1038/nchembio.1071 Ferritin controls iron concentrations by storing Fe(III), but the mechanism by which Fe(II) is bound and trafficked into the protein core after oxidation remains controversial. Spectroscopic methods in combination with labeling and competition assays now define a mechanism conserved from archaea to humans. Top Advertisement Subscribe today to Nature Chemical Biology Reflecting the diversity and excitement of chemical biology research. Subscribe online here today: https://secure.nature.com/subscribe/nchembio   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. 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