Nature Chemical Biology Contents: November 2016, Volume 12 No 11 pp 887 - 987

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 November 2016 Volume 12, Issue 11 Obituary Research Highlights News and Views Brief Communications Articles Advertisement The Naturejobs Career Expo is returning to Düsseldorf.   Friday 18, November 2016 This free career fair offers talented scientists an excellent opportunity to meet a diverse selection of national and international employers from academic institutions and scientific industries, such as pharmaceutical organisations, digital technology companies, science publishing and much more.  Register free today! Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement Springer Nature offers a free open access funding support service to enable authors to discover and apply for article processing charge funding available to them. Visit our website for further advice on the funding options available, and guidance in approaching funders and institutions, or email openaccess@nature.com for more information.   Advertisement Translational Psychiatry is an online-only, open access journal exploring the translational pathway between research in neuroscience and conceptually novel treatments. Explore the benefits of submitting your next research article.   Obituary Top Roger Y. Tsien 1952-2016   p887 Amy E Palmer and Jin Zhang doi:10.1038/nchembio.2213 Roger Tsien left us on August 24. His untimely passing has saddened and shocked the scientific community. Roger literally and figuratively brightened our world, illuminated the dark matter of biology, and forever changed our view of the interface of chemistry and biology. Research Highlights Top Proteomics: Fishing for zinc | Insulin signaling: At a snail's pace | Synthetic biology: Cholera detectors | Long non-coding RNAs: Pulsating RNA motifs News and Views Top Protein dynamics: Conformational footprints   pp890 - 891 Buyong Ma and Ruth Nussinov doi:10.1038/nchembio.2212 The mechanisms by which proteins evolve new functions can be slow and mysterious. Comprehensive structural analysis of enzyme variants reveal how gradual enrichments of pre-existing populations with the right productive dynamics for new functions can accomplish this aim. See also: Article by Campbell et al. Antibiotics: New recipe for targeting resistance   pp891 - 892 Balazs Papp and Viktoria Lazar doi:10.1038/nchembio.2215 The rapid spread of antibiotic-resistant bacteria demands novel treatment approaches that delay or even reverse the evolution of resistance. A new screening strategy identifies two compounds that select against a common tetracycline-resistance gene in Escherichia coli. See also: Brief Communication by Stone et al. Enzyme mechanisms: Sugary shears   pp892 - 893 Ethan D Goddard-Borger doi:10.1038/nchembio.2216 Proteolytic maturation of an important transcriptional regulator is performed by a glycosyltransferase. The reaction involves glycosylation of a glutamate residue and conversion of the [gamma]-glycosyl ester product into an N-acyl pyroglutamate, which undergoes spontaneous hydrolysis to effect peptide backbone fission. See also: Brief Communication by Janetzko et al. Metabolic engineering: Biosensors get the green light   pp894 - 895 Sarah K Hammer and Jose L Avalos doi:10.1038/nchembio.2214 A novel approach recruits the largest prokaryotic family of ligand-induced transcriptional regulators to develop a new class of biosensors in yeast based on transcriptional activation, vastly expanding the repertoire of biosensors that could function in eukaryotic hosts. See also: Article by Skjoedt et al. Chemical Biology JOBS of the week Tenure-Track Assistant Professor in Chemical Biology The Carlson School of Chemistry and Biochemistry at Clark University Assistant Professor Chemistry and Chemical Biology Vanderbilt University More Science jobs from Brief Communications Top Small-molecule WNK inhibition regulates cardiovascular and renal function   pp896 - 898 Ken Yamada, Hyi-Man Park, Dean F Rigel, Keith DiPetrillo, Erin J Whalen et al. doi:10.1038/nchembio.2168 A selective inhibitor of the With-No-Lysine (K) (WNK) kinase family reduces blood pressure and increases electrolyte excretion in hypertensive rats. Chemical compounds How the glycosyltransferase OGT catalyzes amide bond cleavage   pp899 - 901 John Janetzko, Sunia A Trauger, Michael B Lazarus and Suzanne Walker doi:10.1038/nchembio.2173 The glycosyltransferase OGT cleaves a substrate, HCF-1, via a glutamyl-sugar intermediate, defining a reaction mechanism that requires UDP-GlcNAc and involves the formation of an internal pyroglutamate that undergoes spontaneous backbone hydrolysis. See also: News and Views by Goddard-Borger Compounds that select against the tetracycline-resistance efflux pump   pp902 - 904 Laura K Stone, Michael Baym, Tami D Lieberman, Remy Chait, Jon Clardy et al. doi:10.1038/nchembio.2176 A high-throughput screen against the E. coli tetracycline-resistance efflux pump TetA identifies two 'selection-inverting' compounds that swap tetracycline resistance for resistance to another antibiotic, paving the way for two-phase antibiotic treatment protocols. See also: News and Views by Papp & Lazar Carbon extension in peptidylnucleoside biosynthesis by radical SAM enzymes   pp905 - 907 Edward A Lilla and Kenichi Yokoyama doi:10.1038/nchembio.2187 Nikkomycins and polyoxins are peptidylnucleosides with antifungal activity. The biosynthetic routes to these natural products share a bicyclic intermediate formed by a carbon radical-centered ring closure catalyzed by the radical SAM enzymes NikJ or PolH. Chemical compounds Thermal profiling reveals phenylalanine hydroxylase as an off-target of panobinostat   pp908 - 910 Isabelle Becher, Thilo Werner, Carola Doce, Esther A Zaal, Ina Togel et al. doi:10.1038/nchembio.2185 A chemoproteomics approach utilizing the thermal shift assay and quantitative MS resulted in the identification of phenylalanine hydroxylase as an off-target of the histone deacetylase inhibitor panobinostat. Chemical compounds Advertisement Need access to Nature Plants at your workplace or institution? Site license access offers full online content plus added benefits! Recommend site license access to your librarian.   Articles Top YidC assists the stepwise and stochastic folding of membrane proteins   pp911 - 917 Tetiana Serdiuk, Dhandayuthapani Balasubramaniam, Junichi Sugihara, Stefania A Mari, H Ronald Kaback et al. doi:10.1038/nchembio.2169 An AFM-based single-molecule approach shows how the chaperone and insertase YidC stabilizes E. coli LacY in the unfolded state and assists LacY to insert and fold transmembrane structural segments in random order until folding of the native state is complete. Simultaneous analysis of enzyme structure and activity by kinetic capillary electrophoresis-MS   pp918 - 922 Gleb G Mironov, Christopher M Clouthier, Abdullah Akbar, Jeffrey W Keillor and Maxim V Berezovski doi:10.1038/nchembio.2170 Combining the kinetic separation capability of capillary electrophoresis with the structural elucidation capacity of ion-mobility mass spectrometry, a coupled CE-UV-IM-MS system demonstrates utility in examining transglutaminase conformers and their enzymatic activity. Chemical compounds Overcoming resistance to HER2 inhibitors through state-specific kinase binding   pp923 - 930 Chris J Novotny, Sirkku Pollari, Jin H Park, Mark A Lemmon, Weijun Shen et al. doi:10.1038/nchembio.2171 High-throughput screening identified a small-molecule compound that targets the active conformation of HER2 and is effective against growth-factor-mediated drug resistance. Chemical compounds Inhibition of Mcl-1 through covalent modification of a noncatalytic lysine side chain   pp931 - 936 Gizem Akcay, Matthew A Belmonte, Brian Aquila, Claudio Chuaqui, Alexander W Hird et al. doi:10.1038/nchembio.2174 The use of an aryl boronic acid carbonyl warhead to target a noncatalytic lysine side chain enables the development of covalent inhibitors against the anti-apoptotic protein myeloid cell leukemia 1 (Mcl-1). Chemical compounds Lactate metabolism is associated with mammalian mitochondria   pp937 - 943 Ying-Jr Chen, Nathaniel G Mahieu, Xiaojing Huang, Manmilan Singh, Peter A Crawford et al. doi:10.1038/nchembio.2172 The application of high-resolution metabolomics integrated with isotope labeling revealed that lactate is imported into the mitochondria and is metabolized by mitochondrial LDH into pyruvate. The role of protein dynamics in the evolution of new enzyme function   pp944 - 950 Eleanor Campbell, Miriam Kaltenbach, Galen J Correy, Paul D Carr, Benjamin T Porebski et al. doi:10.1038/nchembio.2175 Analysis of the structures and dynamics of intermediates and engineered mutants from directed protein evolution experiments reveals how dynamic conformational changes are harnessed across evolutionary trajectories to generate new catalytic functions. See also: News and Views by Ma & Nussinov Engineering prokaryotic transcriptional activators as metabolite biosensors in yeast   pp951 - 958 Mette L Skjoedt, Tim Snoek, Kanchana R Kildegaard, Dushica Arsovska, Michael Eichenberger et al. doi:10.1038/nchembio.2177 Transplantation of the prokaryotic LysR-type transcriptional regulator into yeast combined with in vivo screening identifies yeast mutants that produce metabolic products with bacterial small molecule inducers. See also: News and Views by Hammer & Avalos Ultra-deep tyrosine phosphoproteomics enabled by a phosphotyrosine superbinder   pp959 - 966 Yangyang Bian, Lei Li, Mingming Dong, Xuguang Liu, Tomonori Kaneko et al. doi:10.1038/nchembio.2178 A SH2-domain-derived superbinder that exhibits strong affinity for phosphotyrosine (pTyr) was used in conjugation with mass spectroscopy approaches to enrich and enable identification of pTyr sites in different cancer cell lines. Amino-group carrier-protein-mediated secondary metabolite biosynthesis in Streptomyces   pp967 - 972 Fumihito Hasebe, Kenichi Matsuda, Taro Shiraishi, Yushi Futamura, Takeshi Nakano et al. doi:10.1038/nchembio.2181 Vzb22, an amino-group carrier protein from Streptomyces, is required for biosynthesis of the noncanonical amino acid DADH, a biosynthetic precursor of vazabitide A and related azabicyclohexane natural products. Chemical compounds Structural basis for precursor protein-directed ribosomal peptide macrocyclization   pp973 - 979 Kunhua Li, Heather L Condurso, Gengnan Li, Yousong Ding and Steven D Bruner doi:10.1038/nchembio.2200 Biosynthesis of the protease inhibitor microviridin J includes peptide macrocyclization catalyzed by two enzymes of the ATP-grasp family. Structures of these macrocyclases, MdnB and MdnC, reveal how they recognize their precursor-peptide substrates. A chemical-inducible CRISPR-Cas9 system for rapid control of genome editing   pp980 - 987 Kaiwen Ivy Liu, Muhammad Nadzim Bin Ramli, Cheok Wei Ariel Woo, Yuanming Wang, Tianyun Zhao et al. doi:10.1038/nchembio.2179 A modified version of Cas9 with a fusion of the hormone-binding domain of the estrogen receptor allows reversible control of Cas9 activity with high efficiency at multiple loci with 4-hydroxytamoxifen treatment. Advertisement Nature Reviews Chemistry — Stay Informed The second physical sciences title in the Nature Reviews portfolio, Nature Reviews Chemistry aims to build on the success of Nature Chemistry and emulate the principles of authoritative, high-quality content and exceptional editorial standards that are the hallmark of the Nature Reviews titles. Register for the Nature Reviews Chemistry e-alert and stay informed about the latest news and research in topics covering the breadth of pure and applied chemistry. Sign up for the e-alert   Top Advertisement nature.com webcasts Join us for our upcoming webcast with live Q&A:  INNOVATING FOR OPHTHALMIC DISEASES Presented by BioPharma Dealmakers Date: Thursday, October 20, 2016 Time: 7am PDT / 10am EDT / 3pm BST / 4pm CEST  REGISTER FOR FREE   Sponsored by: HEALIOS K.K. | Apellis | Mannin Research     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.