Nature Chemical Biology Contents: August 2015, Volume 11 No 8 pp 533 - 617

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TABLE OF CONTENTS August 2015 Volume 11, Issue 8 Editorial Correspondence Commentaries Q&A Research Highlights News and Views Brief Communication Articles Subscribe   Facebook   RSS   Recommend to library   Twitter   Editorial Top Probing questions   p533 doi:10.1038/nchembio.1882 Chemical probes are proven tools for biological research and early-stage drug development, but how can chemical biologists make them more useful to the broader scientific community? Correspondence Top Curation of chemogenomics data   p535 Denis Fourches, Eugene Muratov and Alexander Tropsha doi:10.1038/nchembio.1881 Commentaries Top The promise and peril of chemical probes   pp536 - 541 Cheryl H Arrowsmith, James E Audia, Christopher Austin, Jonathan Baell, Jonathan Bennett et al. doi:10.1038/nchembio.1867 Chemical probes are powerful reagents with increasing impacts on biomedical research. However, probes of poor quality or that are used incorrectly generate misleading results. To help address these shortcomings, we will create a community-driven wiki resource to improve quality and convey current best practice. Probing the epigenome   pp542 - 545 Andrea Huston, Cheryl H Arrowsmith, Stefan Knapp and Matthieu Schapira doi:10.1038/nchembio.1871 Epigenetic chemical probes are having a strong impact in biological discovery and target validation. Systematic coverage of emerging epigenetic target classes with these potent, selective, cell-active chemical tools will profoundly influence understanding of the human biology and pathology of chromatin-templated mechanisms. Q&A Top Voices of chemical biology   pp546 - 547 doi:10.1038/nchembio.1880 We asked a collection of chemical biologists: "What is the most significant challenge facing chemical biology as a discipline?" Research Highlights Top Protein regulation: Inteins under wraps | Lipid metabolism: Working out SCD's kinks | Antibacterials: Clamping down on Mtb | Plant development: Fighting for space | Photopharmacology: Microtubules see the light | Protein phosphorylation: KISSing kinases News and Views Top DNA replication: Unlocking the secrets of fork arrest   pp550 - 551 Jun Fan and Terence R Strick doi:10.1038/nchembio.1860 A powerful, high-throughput single-molecule approach to probe the nanoscale mechanical properties of the Tus-Ter protein-DNA complex reveals that the Tus-Ter-induced lock in unzipping at the nonpermissive face requires only DNA strand separation and involves a progressive strengthening of the Tus-Ter complex. See also: Article by Berghuis et al. Biosynthesis: Leading the way to RiPPs   pp551 - 552 A James Link doi:10.1038/nchembio.1862 Many peptide-based natural products require a leader peptide to reach their final modified form, but the identification of general rules for leader peptide interactions have been stymied by the diversity of these molecules. Two papers reporting crystallographic and bioinformatic analysis of these systems now reveal a structurally conserved domain that mediates leader peptide binding. Epigenetics: Disrupting histone lysine methylation   pp552 - 554 Patrick Trojer doi:10.1038/nchembio.1861 A small molecule targeting the protein-protein interaction between a chromatin binding protein and an oncogenic transcription factor shows therapeutic potential in a subtype of acute myeloid leukemia. See also: Article by Grebien et al. Chemical Biology JOBS of the week Research Associate in Chemical Biology and Biocatalysis The University of Manchester PhD in Systems Biology - Metabolic Modeling Eawag, Swiss Federal Institute of Aquatic Science and Technology Tenure Track Position at the Department of Applied Biological Chemistry Department of Applied Biological Chemistry, Faculty of Agriculture of Shizuoka University More Science jobs from Chemical Biology EVENT Autumn School Chemical Biology 5-9 October 2015 Konstanz, Germany More science events from Brief Communication Top 5-Formylcytosine can be a stable DNA modification in mammals   pp555 - 557 Martin Bachman, Santiago Uribe-Lewis, Xiaoping Yang, Heather E Burgess, Mario Iurlaro et al. doi:10.1038/nchembio.1848 5-Formylcytosine (5fC), produced by TET-mediated oxidation of 5-methylcytosine, is considered an intermediate in active DNA demethylation. Labeling studies and LC/MS analysis across mouse developmental stages reveals that 5fC modifications are more persistent in the genome and may have other functional roles. Advertisement Nature Communications is now fully open access All new submissions if accepted, will be published open access and an article processing charge will apply. For more information visit the website. Visit our open access funding page or contact openaccess@nature.com to learn more on APC funding.   Articles Top Structural analysis of leader peptide binding enables leader-free cyanobactin processing   pp558 - 563 Jesko Koehnke, Greg Mann, Andrew F Bent, Hannes Ludewig, Sally Shirran et al. doi:10.1038/nchembio.1841 Structural and biochemical analysis of the heterocyclase that acts on a ribosomally synthesized and post-translationally modified peptide identifies the basis for leader peptide activation and facilitates engineering of a constitutively active enzyme. A prevalent peptide-binding domain guides ribosomal natural product biosynthesis   pp564 - 570 Brandon J Burkhart, Graham A Hudson, Kyle L Dunbar and Douglas A Mitchell doi:10.1038/nchembio.1856 Bioinformatic and biochemical analyses define a conserved domain present in the biosynthetic clusters for ribosomally synthesized and post-translationally modified peptides (RiPPs) that recognizes the leader peptide and thus controls downstream processing. Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia   pp571 - 578 Florian Grebien, Masoud Vedadi, Matthaus Getlik, Roberto Giambruno, Amit Grover et al. doi:10.1038/nchembio.1859 The p30 isoform of C/EBPα associated with leukemia interacts with WDR5, a component of the SET/MLL histone methyltransferase complex. A small molecule, OICR-9429, disrupted p30-WDR5 interactions, resulting in differentiation of p30-expressing leukemia cells. Chemical compounds See also: News and Views by Trojer Strand separation establishes a sustained lock at the Tus-Ter replication fork barrier   pp579 - 585 Bojk A Berghuis, David Dulin, Zhi-Qiang Xu, Theo van Laar, Bronwen Cross et al. doi:10.1038/nchembio.1857 Tus protein bound to Ter sites on circular bacterial chromosomes provides a way to avoid random crashes of opposing replication forks. DNA-unzipping experiments show that the Tus-Ter-induced lock during unzipping at the nonpermissive face requires only DNA-strand separation. See also: News and Views by Fan & Strick Structural basis of enzymatic benzene ring reduction   pp586 - 591 Tobias Weinert, Simona G Huwiler, Johannes W Kung, Sina Weidenweber, Petra Hellwig et al. doi:10.1038/nchembio.1849 Structural, spectroscopic and kinetic analyses suggest that class II benzoyl-CoA reductases from anaerobic bacteria use an unusual tungsten cofactor and a conserved histidine to perform a reduction akin to the widely used Birch reduction in organic chemistry. Chemical pulldown reveals dynamic pseudouridylation of the mammalian transcriptome   pp592 - 597 Xiaoyu Li, Ping Zhu, Shiqing Ma, Jinghui Song, Jinyi Bai et al. doi:10.1038/nchembio.1836 Pseudouridine (ψ) is a C-linked uracil modification originally discovered in tRNA. MS analysis and CeU-Seq, a method that permits chemical tagging, pulldown and sequencing of [psi] residues, reveal that these modifications are more abundant in the mammalian transcriptome than previously thought. Chemical compounds Control of carotenoid biosynthesis through a heme-based cis-trans isomerase   pp598 - 605 Jesus Beltran, Brian Kloss, Jonathan P Hosler, Jiafeng Geng, Aimin Liu et al. doi:10.1038/nchembio.1840 Carotenoid biosynthesis requires isomerization of the central double bond. Informatic, spectroscopic and functional characterization of Z-ISO, a protein involved in the process, demonstrates that it is a standalone enzyme with unusual heme-dependent chemistry. New classes of self-cleaving ribozymes revealed by comparative genomics analysis   pp606 - 610 Zasha Weinberg, Peter B Kim, Tony H Chen, Sanshu Li, Kimberly A Harris et al. doi:10.1038/nchembio.1846 A bioinformatics pipeline guided by genomic hints of where to look led to the identification and validation of several new classes of self-cleaving ribozymes and several catalytic RNA motifs related to the known hammerhead or HDV ribozymes. Catalytic in vivo protein knockdown by small-molecule PROTACs   pp611 - 617 Daniel P Bondeson, Alina Mares, Ian E D Smith, Eunhwa Ko, Sebastien Campos et al. doi:10.1038/nchembio.1858 The use of a high-affinity VHL ligand allows the development of chimeric molecules that promote the association of ERRα or RIPK2 with the VHL E3 ubiquitin ligase complex, resulting in protein degradation. Chemical compounds Top Advertisement Noncoding RNAs in Endocrinology  Noncoding RNAs have important roles in the development and regulation of the endocrine system. This web collection on noncoding RNAs in endocrinology highlights current and future applications of noncoding RNAs as diagnostic and prognostic biomarkers and as therapeutic targets for personalized management of patients with a wide range of endocrine diseases. Access the collection online.     Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. 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