Nature Chemical Biology Contents: October 2016, Volume 12 No 10 pp 763 - 885

If you are unable to see the message below, click here to view.

Advertisement Solve our challenge and win $200,000.  Identify novel small molecules that bind glucose and improve diabetes treatments. Visit our challenge here.  TABLE OF CONTENTS October 2016 Volume 12, Issue 10 Research Highlights News and Views Brief Communications Articles Corrigendum Advertisement nature.com webcasts Springer Nature presents a custom webcast on Pure protein: optimal resin selection to maximize purification efficiency Date: Thursday September 29, 2016 Time: 8AM PDT, 11AM EDT, 4PM BST, 5PM CEST  Register at: An expert panel will answer all your questions regarding resin selection strategies following the webinar. Sponsored by: Thermo Fisher Scientific Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Open for Submissions  A new open access, multi- and interdisciplinary journal dedicated to publishing the highest quality papers on systems biology, the journal is now open for submissions. Explore the benefits of submitting your next research.   Research Highlights Top Host-microbe interactions: DAO does it | Transcriptional regulation: Stuck in traffic | Proteasomes: Attack of cancer drugs | Phospholipids: How to flip a flippase News and Views Top Stapled peptides: How to be quick on the uptake   pp764 - 765 Joshua A Kritzer doi:10.1038/nchembio.2183 Stapled helices are promising compounds for inhibiting intracellular protein-protein interactions, but the discovery of peptides with the key property of cellular uptake has taken place largely through trial and error. A new study defines physicochemical parameters for designing hydrocarbon-stapled helices with a greater likelihood of cellular uptake. See also: Article by Bird et al. Transcriptional kinases: Caught by a sticky drug   pp765 - 766 Dalibor Blazek doi:10.1038/nchembio.2184 A new study reports THZ531 as a covalent CDK12/CDK13 inhibitor affecting transcription. Application of the compound in cells decreases transcription elongation of DNA damage response genes and key super-enhancer-associated transcription factor genes, with important implications for targeted cancer therapy. See also: Article by Zhang et al. Single-molecule biophysics: TALEs spin along, but not around   pp766 - 768 Sebastian Becker and Jens Boch doi:10.1038/nchembio.2182 TALE proteins search for target sequences along a DNA substrate in a uniquely one-dimensional and non-rotating fashion. See also: Article by Cuculis et al. Post-translational modifications: Bonds that bind   pp768 - 769 Marcey L Waters doi:10.1038/nchembio.2186 Scientists find that oxidation of methionine induces favorable interactions with aromatic groups in proteins, contrary to conventional wisdom, providing new molecular insight into the structural and biological impact of methionine oxidation. See also: Article by Lewis et al. Chemical Biology JOBS of the week Postdoctoral Fellow in Chemical Biology University of Houston Chemical Biology Institute Junior Faculty Search Yale University The Chemical Biology Institute Postdoctoral Position in Chemical Biology of Tubulin Modifications Ecole Polytechnique Fédérale de Lausanne (EPFL) Assistant Professor, Chemistry and Chemical Biology Vanderbilt University More Science jobs from Brief Communications Top A hybrid polyketide-nonribosomal peptide in nematodes that promotes larval survival   pp770 - 772 Qingyao Shou, Likui Feng, Yaoling Long, Jungsoo Han, Joshawna K Nunnery et al. doi:10.1038/nchembio.2144 Nemamides are hybrid polyketide-nonribosomal peptide natural products that were identified by metabolomics profiling in Caenorhabditis elegans and are involved in the organism's survival response to nutrient-deficient conditions. Chemical compounds Divergent biosynthesis yields a cytotoxic aminomalonate-containing precolibactin   pp773 - 775 Zhong-Rui Li, Jie Li, Jin-Ping Gu, Jennifer Y H Lai, Brendan M Duggan et al. doi:10.1038/nchembio.2157 Variations in pathway off-loading and module skipping within a hybrid polyketide synthase-nonribosomal peptide synthetase lead to the production of a collection of precursors to colibactin, a genotoxic compound produced by gut bacteria. Chemical compounds Genetic code expansion in the mouse brain   pp776 - 778 Russell J Ernst, Toke P Krogager, Elizabeth S Maywood, Roberto Zanchi, Vaclav Beranek et al. doi:10.1038/nchembio.2160 Adeno-associated viral delivery of an orthogonal tRNA synthetase-tRNA system enables the encoded incorporation of non-natural amino acids into proteins in neuronal cells, in brain slices and in living mice. Chemical compounds Advertisement Need access to Nature Microbiology at your workplace or institution? Site license access offers full online content plus added benefits! Recommend site license access to your librarian.   Articles Top Metabolic plasticity underpins innate and acquired resistance to LDHA inhibition   pp779 - 786 Aaron Boudreau, Hans E Purkey, Anna Hitz, Kirk Robarge, David Peterson et al. doi:10.1038/nchembio.2143 The application of a potent lactate dehydrogenase (LDHA) inhibitor GNE-140 on pancreatic cancer cells revealed that resistance to GNE-140 is attributable to an AMPK-mTOR-S6K-mediated switch in utilization from glycolysis to oxidative phosphorylation. Chemical compounds An histidine covalent receptor and butenolide complex mediates strigolactone perception   pp787 - 794 Alexandre de Saint Germain, Guillaume Clave, Marie-Ange Badet-Denisot, Jean-Paul Pillot, David Cornu et al. doi:10.1038/nchembio.2147 Analysis of the hydrolysis kinetics of strigolactone receptors using enzyme-activated fluorescent probes revealed that the catalytic triad histidine of the receptor forms a covalent interaction with the strigolactone hydrolysis product, the D ring. Chemical compounds Inhibiting androgen receptor nuclear entry in castration-resistant prostate cancer   pp795 - 801 Julie A Pollock, Suzanne E Wardell, Alexander A Parent, David B Stagg, Stephanie J Ellison et al. doi:10.1038/nchembio.2131 A cyclobutane compound competitively inhibits the activity of androgen receptors (AR) containing antiandrogen-resistant mutations through stabilization of the receptor in an apo-like conformation and preventing AR nuclear entry. Chemical compounds FRET binding antenna reports spatiotemporal dynamics of GDI-Cdc42 GTPase interactions   pp802 - 809 Louis Hodgson, Desiree Spiering, Mohsen Sabouri-Ghomi, Onur Dagliyan, Celine DerMardirossian et al. doi:10.1038/nchembio.2145 The modification of Cdc42 with a FRET binding antenna (GDI.Cdc42 FLARE) enables detection of Cdc42 binding to guanine-nucleotide dissociation inhibitor (GDI) and Cdc42 activation with improved spatial-temporal resolution during cellular protrusion and retraction. Structural basis of laminin binding to the LARGE glycans on dystroglycan   pp810 - 814 David C Briggs, Takako Yoshida-Moriguchi, Tianqing Zheng, David Venzke, Mary E Anderson et al. doi:10.1038/nchembio.2146 The LARGE glycosyltransferase generates a repeating disaccharide on α-dystroglycan, an extracellular matrix receptor essential for muscle function. A structural study defines a unique binding mode between the LARGE-generated oligosaccharide and the matrix protein laminin. Cellularly active N-hydroxyurea FEN1 inhibitors block substrate entry to the active site   pp815 - 821 Jack C Exell, Mark J Thompson, L David Finger, Steven J Shaw, Judit Debreczeni et al. doi:10.1038/nchembio.2148 Structural, enzymatic and cellular target engagement studies reveal the mechanism of action by N-hydroxyurea small molecule inhibitors of the DNA repair enzyme, human flap endonuclease-1 (FEN1) that prevent cleavage of DNA flaps in cancer cells. Chemical compounds Discovery of allosteric modulators for GABAA receptors by ligand-directed chemistry   pp822 - 830 Kei Yamaura, Shigeki Kiyonaka, Tomohiro Numata, Ryuji Inoue and Itaru Hamachi doi:10.1038/nchembio.2150 A biosensor based on the GABAA receptor with a readout consisting of quenching and recovery of biomolecular fluorescence in live cells is used in a screen to identify new interacting ligands for the receptor benzodiazepine site. Chemical compounds TALE proteins search DNA using a rotationally decoupled mechanism   pp831 - 837 Luke Cuculis, Zhanar Abil, Huimin Zhao and Charles M Schroeder doi:10.1038/nchembio.2152 A single-molecule approach demonstrates that TALEs scan DNA using a unique 'zip-line' mechanism wherein the TALEs move without rotating along the DNA helix, yet the DNA remains threaded through the loosely wrapped TALE. See also: News and Views by Becker & Boch Discovery of LRE1 as a specific and allosteric inhibitor of soluble adenylyl cyclase   pp838 - 844 Lavoisier Ramos-Espiritu, Silke Kleinboelting, Felipe A Navarrete, Antonio Alvau, Pablo E Visconti et al. doi:10.1038/nchembio.2151 A high-throughput screen using a mass-spectrometry-based assay results in the identification of LRE1 as an inhibitor of HCO3-/Ca2+-regulated soluble adenylyl cyclase activity. LRE1 interacts with the HCO3- binding site (BBS) to block cAMP formation. Chemical compounds Biophysical determinants for cellular uptake of hydrocarbon-stapled peptide helices   pp845 - 852 Gregory H Bird, Emanuele Mazzola, Kwadwo Opoku-Nsiah, Margaret A Lammert, Marina Godes et al. doi:10.1038/nchembio.2153 Detailed biophysical, microscopy, and statistical analyses of hydrocarbon-stapled peptide variants revealed how a combination of critical parameters such as hydrophobicity, [alpha]-helicity and isoelectric point influence cellular permeability. See also: News and Views by Kritzer Fluorogenic probes reveal a role of GLUT4 N-glycosylation in intracellular trafficking   pp853 - 859 Shinya Hirayama, Yuichiro Hori, Zsolt Benedek, Tadashi Suzuki and Kazuya Kikuchi doi:10.1038/nchembio.2156 Probes based on the photoactive yellow protein tag for monitoring the consequences of glycosylation on GLUT4 traffic reveal that glycosylation is important for plasma membrane retention of the glucose transporter. Chemical compounds Oxidation increases the strength of the methionine-aromatic interaction   pp860 - 866 Andrew K Lewis, Katie M Dunleavy, Tiffany L Senkow, Cheng Her, Benjamin T Horn et al. doi:10.1038/nchembio.2159 A combination of statistical analysis, quantum mechanics calculations and biophysical analytical approaches shows that methionine oxidation increases its interactions with aromatic side chains, interactions that are important for intraprotein and interprotein interactions. See also: News and Views by Waters Dual action antifungal small molecule modulates multidrug efflux and TOR signaling   pp867 - 875 Tanvi Shekhar-Guturja, G M Kamal B Gunaherath, E M Kithsiri Wijeratne, Jean-Philippe Lambert, Anna F Averette et al. doi:10.1038/nchembio.2165 Biochemical and genetic strategies demonstrate that the antifungal natural product beauvericin targets both multidrug efflux and TOR signaling to limit drug resistance and to sensitize resistant pathogens to drug treatment during infection. Chemical compounds Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors   pp876 - 884 Tinghu Zhang, Nicholas Kwiatkowski, Calla M Olson, Sarah E Dixon-Clarke, Brian J Abraham et al. doi:10.1038/nchembio.2166 A small molecule inhibits CDK12 and CDK13 activity through covalent modification of Cys residues and reveals a role of the two kinases in regulating Pol II processivity and super-enhancer-driven transcription factor and DNA damage response gene expression. Chemical compounds See also: News and Views by Blazek Advertisement Nature Insight: The Protein World This Insight highlights four exciting topics in contemporary protein science: de novo designed proteins; how cells monitor and regulate the proteome; the rise of cryo-electron microscopy; and proteome analysis through high-resolution mass spectrometry.     Corrigendum Top Corrigendum: Structural biology: HDAC6 finally crystal clear   p885 Yanli Liu, Li Li and Jinrong Min doi:10.1038/nchembio1016-885 Top 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

You have been sent this Table of Contents Alert because you have opted in to receive it. You can change or discontinue your e-mail alerts at any time, by modifying your preferences on your nature.com account at: www.nature.com/myaccount (You will need to log in to be recognised as a nature.com registrant) For further technical assistance, please contact our registration department For print subscription enquiries, please contact our subscription department For other enquiries, please contact our customer feedback department Nature Publishing Group | One New York Plaza, Suite 4500 | New York | NY 10004-1562 | USA Nature Publishing Group's worldwide offices: London - Paris - Munich - New Delhi - Tokyo - Melbourne San Diego - San Francisco - Washington - New York - Boston Macmillan Publishers Limited is a company incorporated in England and Wales under company number 785998 and whose registered office is located at The Campus, 4 Crinan Street, London, N1 9XW. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.