Accelerating the semisynthesis of alkaloid-based drugs through metabolic engineering

Posted on Feb 15th, 2017 - By Amy M Ehrenworth

Nature Chemical Biology 13, 249 (2017). doi:10.1038/nchembio.2308 Authors: Amy M Ehrenworth & Pamela…

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mRNA localization: If you have to ASH

Posted on Feb 15th, 2017 - By Joshua M. Finkelstein

Nature Chemical Biology 13, 243 (2017). doi:10.1038/nchembio.2323 Author: Joshua M.…

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Synthetic biology: Synthetic gene networks that smell

Posted on Feb 15th, 2017 - By Fahim Farzadfard

Nature Chemical Biology 13, 245 (2017). doi:10.1038/nchembio.2315 Authors: Fahim Farzadfard & Timothy K Lu Bioengineers have endowed a consortium of human cells with an artificial sense of smell, enabling the cells to detect, quantify, and remember the presence of gaseous volatile compounds in their…

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Enzyme mechanisms: Fickle about fluorine

Posted on Feb 15th, 2017 - By Caitlin Deane

Nature Chemical Biology 13, 243 (2017). doi:10.1038/nchembio.2324 Author: Caitlin…

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Plant infection: A decoy tactic

Posted on Feb 15th, 2017 - By Grant Miura

Nature Chemical Biology 13, 243 (2017). doi:10.1038/nchembio.2322 Author: Grant…

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Metabolism: A-way with biofilms

Posted on Feb 15th, 2017 - By Mirella Bucci

Nature Chemical Biology 13, 243 (2017). doi:10.1038/nchembio.2325 Author: Mirella…

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G-Protein-coupled receptors: Decoding mixed signals

Posted on Feb 15th, 2017 - By Thomas J Gardella

Nature Chemical Biology 13, 247 (2017). doi:10.1038/nchembio.2316 Author: Thomas J Gardella A new mechanism of functional crosstalk between two distinct G-protein-coupled receptors (GPCRs)—the parathyroid hormone receptor (PTHR) and β2-adrenergic receptor (β2 Ar)—that occurs at the level of G protein βγ subunits and a specific adenylyl cyclase isoform is identified. This crosstalk augments cAMP signaling by the PTHR from endosomes, and thus…

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Redox regulation: Taking AKTion on HNEs

Posted on Jan 23rd, 2017 - By Eranthie Weerapana

Nature Chemical Biology 13, 244 (2017). doi:10.1038/nchembio.2311 Author: Eranthie Weerapana Differential redox regulation of kinase isoforms serves to provide intricate control of cellular signaling events. In a new study, a single isoform of Akt, Akt3, is shown to be preferentially modified by lipid-derived electrophiles to modulate downstream signaling events in mammalian cells and…

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The SUV4-20 inhibitor A-196 verifies a role for epigenetics in genomic integrity

Posted on Jan 23rd, 2017 - By Kenneth D Bromberg

Nature Chemical Biology 13, 317 (2017). doi:10.1038/nchembio.2282 Authors: Kenneth D Bromberg, Taylor R H Mitchell, Anup K Upadhyay, Clarissa G Jakob, Manisha A Jhala, Kenneth M Comess, Loren M Lasko, Conglei Li, Creighton T Tuzon, Yujia Dai, Fengling Li, Mohammad S Eram, Alexander Nuber, Niru B Soni, Vlasios Manaves, Mikkel A Algire, Ramzi F Sweis, Maricel Torrent, Gunnar Schotta, Chaohong Sun, Michael R Michaelides, Alex R Shoemaker, Cheryl H Arrowsmith, Peter J Brown,…

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Akt3 is a privileged first responder in isozyme-specific electrophile response

Posted on Jan 23rd, 2017 - By Marcus J C Long

Nature Chemical Biology 13, 333 (2017). doi:10.1038/nchembio.2284 Authors: Marcus J C Long, Saba Parvez, Yi Zhao, Sanjna L Surya, Yiran Wang, Sheng Zhang & Yimon…

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Enzyme-catalyzed cationic epoxide rearrangements in quinolone alkaloid biosynthesis

Posted on Jan 23rd, 2017 - By Yi Zou

Nature Chemical Biology 13, 325 (2017). doi:10.1038/nchembio.2283 Authors: Yi Zou, Marc Garcia-Borràs, Mancheng C Tang, Yuichiro Hirayama, Dehai H Li, Li Li, Kenji Watanabe, K N Houk & Yi…

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Synthetic biology: Sensing with modular receptors

Posted on Jan 19th, 2017 - By Matthew Brenner

Nature Chemical Biology 13, 131 (2017). doi:10.1038/nchembio.2290 Authors: Matthew Brenner, Jang Hwan Cho & Wilson W Wong Sensing and responding to diverse extracellular signals is a crucial aspect of cellular decision-making that is currently lacking in the synthetic biology toolkit. The development of modular receptor platforms allows for the rewiring of cellular input–output…

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Susan Lindquist (1949–2016)

Posted on Jan 19th, 2017 - By Tricia R Serio

Nature Chemical Biology 13, 127 (2017). doi:10.1038/nchembio.2305 Author: Tricia R Serio Susan Lindquist passed away on 27 October 2016, far too early for those who marveled at her brilliance through her many contributions to science, for all who knew her directly, and especially for her former…

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RNA modification: Reading Sex-lethal

Posted on Jan 19th, 2017 - By Grant Miura

Nature Chemical Biology 13, 129 (2017). doi:10.1038/nchembio.2291 Author: Grant…

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Nitrogenase: A fuel-producing microbe

Posted on Jan 19th, 2017 - By Holger Dobbek

Nature Chemical Biology 13, 134 (2017). doi:10.1038/nchembio.2288 Author: Holger Dobbek Nitrogenase has the canonical ability to reduce N2 to NH3, but under certain conditions, either in vitro or in vivo, it has the additional capability to convert CO2 to CO and CO to light…

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Biosynthesis: Terrifically tailored peptides

Posted on Jan 19th, 2017 - By Caitlin Deane

Nature Chemical Biology 13, 129 (2017). doi:10.1038/nchembio.2292 Author: Caitlin…

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Host-Pathogen interactions: Nucleotide circles of life and death

Posted on Jan 19th, 2017 - By Lingyin Li

Nature Chemical Biology 13, 130 (2017). doi:10.1038/nchembio.2289 Author: Lingyin Li A phosphodiesterase, CdnP, from Mycobacterium tuberculosis (M. tb.) helps the pathogen evade immune detection by degrading the second messenger cyclic di-AMP that alerts the host to its presence. Genetic knockout of CdnP dampens the virulence of the pathogen, suggesting that CdnP inhibitors are potential anti–M. tb.…

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Pancreatic development: Changing identity

Posted on Jan 19th, 2017 - By Grant Miura

Nature Chemical Biology 13, 129 (2017). doi:10.1038/nchembio.2293 Author: Grant…

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Target engagement: Shining a light

Posted on Jan 19th, 2017 - By Kilian V M Huber

Nature Chemical Biology 13, 133 (2017). doi:10.1038/nchembio.2295 Author: Kilian V M Huber The ability to measure the binding of a compound to its intended target in live cells or tissue is a critical parameter for drug discovery. A new method using polarized light microscopy adds to the current toolbox by enabling monitoring of target engagement in vitro and in vivo at single-cell…

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RNA structure: Untying Zika’s knots

Posted on Jan 19th, 2017 - By Terry L. Sheppard

Nature Chemical Biology 13, 129 (2017). doi:10.1038/nchembio.2294 Author: Terry L.…

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The pharmacological regulation of cellular mitophagy

Posted on Jan 19th, 2017 - By Nikolaos D Georgakopoulos

Nature Chemical Biology 13, 136 (2017). doi:10.1038/nchembio.2287 Authors: Nikolaos D Georgakopoulos, Geoff Wells & Michelangelo…

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Recurrent RNA motifs as scaffolds for genetically encodable small-molecule biosensors

Posted on Jan 16th, 2017 - By Ely B Porter

Nature Chemical Biology 13, 295 (2017). doi:10.1038/nchembio.2278 Authors: Ely B Porter, Jacob T Polaski, Makenna M Morck & Robert T…

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Chemical proteomics reveals ADP-ribosylation of small GTPases during oxidative stress

Posted on Jan 16th, 2017 - By Nathan P Westcott

Nature Chemical Biology 13, 302 (2017). doi:10.1038/nchembio.2280 Authors: Nathan P Westcott, Joseph P Fernandez, Henrik Molina & Howard C…

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Lysine relay mechanism coordinates intermediate transfer in vitamin B6 biosynthesis

Posted on Jan 16th, 2017 - By Matthew J Rodrigues

Nature Chemical Biology 13, 290 (2017). doi:10.1038/nchembio.2273 Authors: Matthew J Rodrigues, Volker Windeisen, Yang Zhang, Gabriela Guédez, Stefan Weber, Marco Strohmeier, Jeremiah W Hanes, Antoine Royant, Gwyndaf Evans, Irmgard Sinning, Steven E Ealick, Tadhg P Begley & Ivo…

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Designed cell consortia as fragrance-programmable analog-to-digital converters

Posted on Jan 16th, 2017 - By Marius Müller

Nature Chemical Biology 13, 309 (2017). doi:10.1038/nchembio.2281 Authors: Marius Müller, Simon Ausländer, Andrea Spinnler, David Ausländer, Julian Sikorski, Marc Folcher & Martin…

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Structural and functional insights into asymmetric enzymatic dehydration of alkenols

Posted on Jan 9th, 2017 - By Bettina M Nestl

Nature Chemical Biology 13, 275 (2017). doi:10.1038/nchembio.2271 Authors: Bettina M Nestl, Christopher Geinitz, Stephanie Popa, Sari Rizek, Robert J Haselbeck, Rosary Stephen, Michael A Noble, Max-Philipp Fischer, Erik C Ralph, Hoi Ting Hau, Henry Man, Muhiadin Omar, Johan P Turkenburg, Stephen van Dien, Stephanie J Culler, Gideon Grogan & Bernhard…

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Biomimetic spinning of artificial spider silk from a chimeric minispidroin

Posted on Jan 9th, 2017 - By Marlene Andersson

Nature Chemical Biology 13, 262 (2017). doi:10.1038/nchembio.2269 Authors: Marlene Andersson, Qiupin Jia, Ana Abella, Xiau-Yeen Lee, Michael Landreh, Pasi Purhonen, Hans Hebert, Maria Tenje, Carol V Robinson, Qing Meng, Gustavo R Plaza, Jan Johansson & Anna Rising Herein we present a chimeric recombinant spider silk protein (spidroin) whose aqueous solubility equals that of native spider silk dope and a spinning device that is based solely on aqueous buffers, shear forces and…

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Visualizing the secondary and tertiary architectural domains of lncRNA RepA

Posted on Jan 9th, 2017 - By Fei Liu

Nature Chemical Biology 13, 282 (2017). doi:10.1038/nchembio.2272 Authors: Fei Liu, Srinivas Somarowthu & Anna Marie…

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MraY–antibiotic complex reveals details of tunicamycin mode of action

Posted on Jan 9th, 2017 - By Jonna K Hakulinen

Nature Chemical Biology 13, 265 (2017). doi:10.1038/nchembio.2270 Authors: Jonna K Hakulinen, Jenny Hering, Gisela Brändén, Hongming Chen, Arjan Snijder, Margareta Ek & Patrik Johansson The rapid increase of antibiotic resistance has created an urgent need to develop novel antimicrobial agents. Here we describe the crystal structure of the promising bacterial target phospho-N-acetylmuramoyl–pentapeptide translocase (MraY) in complex with the nucleoside…

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Orthogonal lipid sensors identify transbilayer asymmetry of plasma membrane cholesterol

Posted on Dec 26th, 2016 - By Shu-Lin Liu

Nature Chemical Biology 13, 268 (2017). doi:10.1038/nchembio.2268 Authors: Shu-Lin Liu, Ren Sheng, Jae Hun Jung, Li Wang, Ewa Stec, Matthew J O'Connor, Seohyoen Song, Rama Kamesh Bikkavilli, Robert A Winn, Daesung Lee, Kwanghee Baek, Kazumitsu Ueda, Irena Levitan, Kwang-Pyo Kim & Wonhwa…

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β2-adrenergic receptor control of endosomal PTH receptor signaling via Gβγ

Posted on Dec 26th, 2016 - By Frédéric G Jean-Alphonse

Nature Chemical Biology 13, 259 (2017). doi:10.1038/nchembio.2267 Authors: Frédéric G Jean-Alphonse, Vanessa L Wehbi, Jingming Chen, Masaki Noda, Juan M Taboas, Kunhong Xiao & Jean-Pierre Vilardaga Cells express several G-protein-coupled receptors (GPCRs) at their surfaces, transmitting simultaneous extracellular hormonal and chemical signals into cells. A comprehensive understanding of mechanisms underlying the integrated signaling response induced by distinct…

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Inhibitors of Mycobacterium tuberculosis DosRST signaling and persistence

Posted on Dec 19th, 2016 - By Huiqing Zheng

Nature Chemical Biology 13, 218 (2017). doi:10.1038/nchembio.2259 Authors: Huiqing Zheng, Christopher J Colvin, Benjamin K Johnson, Paul D Kirchhoff, Michael Wilson, Katriana Jorgensen-Muga, Scott D Larsen & Robert B…

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Orphan receptor ligand discovery by pickpocketing pharmacological neighbors

Posted on Dec 19th, 2016 - By Tony Ngo

Nature Chemical Biology 13, 235 (2017). doi:10.1038/nchembio.2266 Authors: Tony Ngo, Andrey V Ilatovskiy, Alastair G Stewart, James L J Coleman, Fiona M McRobb, R Peter Riek, Robert M Graham, Ruben Abagyan, Irina Kufareva & Nicola J…

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Molecular insights into the enzyme promiscuity of an aromatic prenyltransferase

Posted on Dec 19th, 2016 - By Ridao Chen

Nature Chemical Biology 13, 226 (2017). doi:10.1038/nchembio.2263 Authors: Ridao Chen, Bingquan Gao, Xiao Liu, Feiying Ruan, Yong Zhang, Jizhong Lou, Keping Feng, Carsten Wunsch, Shu-Ming Li, Jungui Dai & Fei…

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A fluorescent probe for cysteine depalmitoylation reveals dynamic APT signaling

Posted on Dec 19th, 2016 - By Rahul S Kathayat

Nature Chemical Biology 13, 150 (2017). doi:10.1038/nchembio.2262 Authors: Rahul S Kathayat, Pablo D Elvira & Bryan C Dickinson Hundreds of human proteins are modified by reversible palmitoylation of cysteine residues (S-palmitoylation), but the regulation of depalmitoylation is poorly understood. Here, we develop 'depalmitoylation probes' (DPPs), small-molecule fluorophores, to monitor the endogenous activity levels of 'erasers' of S-palmitoylation, acylprotein thioesterases…

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Protein folding: Minimizing frustration

Posted on Dec 16th, 2016 - By Mirella Bucci

Nature Chemical Biology 13, 1 (2017). doi:10.1038/nchembio.2277 Author: Mirella…

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Biocatalysis: Custom carbon cycling

Posted on Dec 16th, 2016 - By Caitlin Deane

Nature Chemical Biology 13, 1 (2017). doi:10.1038/nchembio.2275 Author: Caitlin…

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Neurodegeneration: Untangling tau

Posted on Dec 16th, 2016 - By Alison Farrell

Nature Chemical Biology 13, 1 (2017). doi:10.1038/nchembio.2276 Author: Alison…

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RNA structure: Widening the probe

Posted on Dec 16th, 2016 - By Grant Miura

Nature Chemical Biology 13, 1 (2017). doi:10.1038/nchembio.2274 Author: Grant…

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Natural products: Mapping an amazing thicket

Posted on Dec 16th, 2016 - By Mark E Horsman

Nature Chemical Biology 13, 6 (2017). doi:10.1038/nchembio.2265 Authors: Mark E Horsman & Christopher N Boddy The Global Natural Products Social Molecular Networking (GNPS) resource and the DEREPLICATOR algorithm provide new tools for analyzing mass spectral data and enabling natural products…

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RAS signaling: Divide and conquer

Posted on Dec 16th, 2016 - By Matthew Holderfield

Nature Chemical Biology 13, 7 (2017). doi:10.1038/nchembio.2264 Authors: Matthew Holderfield & Deborah K Morrison The role of RAS dimerization in tumor biology is an emerging area of preclinical cancer research. Characterization of a RAS monobody indicates that dimer formation is required for RAS signaling, revealing the dimer interface as a potential drug…

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Precise small-molecule recognition of a toxic CUG RNA repeat expansion

Posted on Dec 12th, 2016 - By Suzanne G Rzuczek

Nature Chemical Biology 13, 188 (2017). doi:10.1038/nchembio.2251 Authors: Suzanne G Rzuczek, Lesley A Colgan, Yoshio Nakai, Michael D Cameron, Denis Furling, Ryohei Yasuda & Matthew D…

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Rewiring human cellular input–output using modular extracellular sensors

Posted on Dec 12th, 2016 - By Kelly A Schwarz

Nature Chemical Biology 13, 202 (2017). doi:10.1038/nchembio.2253 Authors: Kelly A Schwarz, Nichole M Daringer, Taylor B Dolberg & Joshua N…

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Single-molecule analysis reveals multi-state folding of a guanine riboswitch

Posted on Dec 12th, 2016 - By Vishnu Chandra

Nature Chemical Biology 13, 194 (2017). doi:10.1038/nchembio.2252 Authors: Vishnu Chandra, Zain Hannan, Huizhong Xu & Maumita…

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Inhibition of innate immune cytosolic surveillance by an M. tuberculosis phosphodiesterase

Posted on Dec 12th, 2016 - By Ruchi Jain Dey

Nature Chemical Biology 13, 210 (2017). doi:10.1038/nchembio.2254 Authors: Ruchi Jain Dey, Bappaditya Dey, Yue Zheng, Laurene S Cheung, Jie Zhou, David Sayre, Pankaj Kumar, Haidan Guo, Gyanu Lamichhane, Herman O Sintim & William R…

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A human microprotein that interacts with the mRNA decapping complex

Posted on Dec 5th, 2016 - By Nadia G D'Lima

Nature Chemical Biology 13, 174 (2017). doi:10.1038/nchembio.2249 Authors: Nadia G D'Lima, Jiao Ma, Lauren Winkler, Qian Chu, Ken H Loh, Elizabeth O Corpuz, Bogdan A Budnik, Jens Lykke-Andersen, Alan Saghatelian & Sarah A…

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Quantitating drug-target engagement in single cells in vitro and in vivo

Posted on Dec 5th, 2016 - By J Matthew Dubach

Nature Chemical Biology 13, 168 (2017). doi:10.1038/nchembio.2248 Authors: J Matthew Dubach, Eunha Kim, Katherine Yang, Michael Cuccarese, Randy J Giedt, Labros G Meimetis, Claudio Vinegoni & Ralph…

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Mutations along a TET2 active site scaffold stall oxidation at 5-hydroxymethylcytosine

Posted on Dec 5th, 2016 - By Monica Yun Liu

Nature Chemical Biology 13, 181 (2017). doi:10.1038/nchembio.2250 Authors: Monica Yun Liu, Hedieh Torabifard, Daniel J Crawford, Jamie E DeNizio, Xing-Jun Cao, Benjamin A Garcia, G Andrés Cisneros & Rahul M…

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Genome-wide chemical mapping of O-GlcNAcylated proteins in Drosophila melanogaster

Posted on Dec 5th, 2016 - By Ta-Wei Liu

Nature Chemical Biology 13, 161 (2017). doi:10.1038/nchembio.2247 Authors: Ta-Wei Liu, Mike Myschyshyn, Donald A Sinclair, Samy Cecioni, Kevin Beja, Barry M Honda, Ryan D Morin & David J…

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Gephyrin-binding peptides visualize postsynaptic sites and modulate neurotransmission

Posted on Nov 28th, 2016 - By Hans Michael Maric

Nature Chemical Biology 13, 153 (2017). doi:10.1038/nchembio.2246 Authors: Hans Michael Maric, Torben Johann Hausrat, Franziska Neubert, Nils Ole Dalby, Sören Doose, Markus Sauer, Matthias Kneussel & Kristian…

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Activation and reduction of carbon dioxide by nitrogenase iron proteins

Posted on Nov 28th, 2016 - By Johannes G Rebelein

Nature Chemical Biology 13, 147 (2017). doi:10.1038/nchembio.2245 Authors: Johannes G Rebelein, Martin T Stiebritz, Chi Chung Lee & Yilin Hu The iron (Fe) proteins of molybdenum (Mo) and vanadium (V) nitrogenases mimic carbon monoxide (CO) dehydrogenase in catalyzing the interconversion between CO2 and CO under ambient conditions. Catalytic reduction of CO2 to CO is achieved in vitro and in vivo upon redox changes of the Fe-protein-associated [Fe4S4] clusters. These…

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Full antagonism of the estrogen receptor without a prototypical ligand side chain

Posted on Nov 21st, 2016 - By Sathish Srinivasan

Nature Chemical Biology 13, 111 (2017). doi:10.1038/nchembio.2236 Authors: Sathish Srinivasan, Jerome C Nwachukwu, Nelson E Bruno, Venkatasubramanian Dharmarajan, Devrishi Goswami, Irida Kastrati, Scott Novick, Jason Nowak, Valerie Cavett, Hai-Bing Zhou, Nittaya Boonmuen, Yuechao Zhao, Jian Min, Jonna Frasor, Benita S Katzenellenbogen, Patrick R Griffin, John A Katzenellenbogen & Kendall W…

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The RNA helicase Mtr4p is a duplex-sensing translocase

Posted on Nov 21st, 2016 - By Eric M Patrick

Nature Chemical Biology 13, 99 (2017). doi:10.1038/nchembio.2234 Authors: Eric M Patrick, Sukanya Srinivasan, Eckhard Jankowsky & Matthew J…

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A computationally engineered RAS rheostat reveals RAS–ERK signaling dynamics

Posted on Nov 21st, 2016 - By John C Rose

Nature Chemical Biology 13, 119 (2017). doi:10.1038/nchembio.2244 Authors: John C Rose, Po-Ssu Huang, Nathan D Camp, Jordan Ye, Andrew M Leidal, Inna Goreshnik, Bridget M Trevillian, Miles S Dickinson, Daniel Cunningham-Bryant, Jayanta Debnath, David Baker, Alejandro Wolf-Yadlin & Dustin J…

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Ubiquitin utilizes an acidic surface patch to alter chromatin structure

Posted on Nov 21st, 2016 - By Galia T Debelouchina

Nature Chemical Biology 13, 105 (2017). doi:10.1038/nchembio.2235 Authors: Galia T Debelouchina, Karola Gerecht & Tom W…

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Nuclear receptors: PPARα ligands make memories

Posted on Nov 15th, 2016 - By Thomas P Burris

Nature Chemical Biology 12, 993 (2016). doi:10.1038/nchembio.2241 Author: Thomas P Burris Three newly identified endogenous ligands of the nuclear receptor PPARα—hydroxydimethylbutyrate, hexadecanamide and octadecenamide—are implicated in the noncanonical activity of PPARα in synaptic function and hippocampal…

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Photosynthesis: Short circuit at the chlorophyll

Posted on Nov 15th, 2016 - By Marc M Nowaczyk

Nature Chemical Biology 12, 990 (2016). doi:10.1038/nchembio.2240 Authors: Marc M Nowaczyk & Nicolas Plumeré Interfacing photosynthetic proteins and electrodes for investigating light-induced charge separation remains challenging. The discovery of a competing charge transfer pathway through the light-harvesting antenna defines new design requirements for electrode…

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Immunology: T cells get L-ARGed

Posted on Nov 15th, 2016 - By Mirella Bucci

Nature Chemical Biology 12, 989 (2016). doi:10.1038/nchembio.2256 Author: Mirella…

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Protein synthesis: Breaking down the NSA1

Posted on Nov 15th, 2016 - By Grant Miura

Nature Chemical Biology 12, 989 (2016). doi:10.1038/nchembio.2258 Author: Grant…

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Epigenomics: Massive ATAC

Posted on Nov 15th, 2016 - By Joshua M. Finkelstein

Nature Chemical Biology 12, 989 (2016). doi:10.1038/nchembio.2257 Author: Joshua M.…

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Drug discovery: Doubling down on BET inhibition

Posted on Nov 15th, 2016 - By Dafydd Owen

Nature Chemical Biology 12, 991 (2016). doi:10.1038/nchembio.2242 Author: Dafydd Owen Through simultaneous binding to more than one site in a single protein, multivalent small molecules can achieve huge increases in potency. This 'avidity effect' has been demonstrated in BET bromodomain-containing proteins with bivalent probes that represent some of the most potent BET inhibitors to…

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RNA structure: Know when to fold ’em

Posted on Nov 15th, 2016 - By Grant Miura

Nature Chemical Biology 12, 989 (2016). doi:10.1038/nchembio.2255 Author: Grant…

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ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition

Posted on Nov 14th, 2016 - By Sebastian Doll

Nature Chemical Biology 13, 91 (2017). doi:10.1038/nchembio.2239 Authors: Sebastian Doll, Bettina Proneth, Yulia Y Tyurina, Elena Panzilius, Sho Kobayashi, Irina Ingold, Martin Irmler, Johannes Beckers, Michaela Aichler, Axel Walch, Holger Prokisch, Dietrich Trümbach, Gaowei Mao, Feng Qu, Hulya Bayir, Joachim Füllekrug, Christina H Scheel, Wolfgang Wurst, Joel A Schick, Valerian E Kagan, José Pedro Friedmann Angeli & Marcus…

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Tunable thermal bioswitches for in vivo control of microbial therapeutics

Posted on Nov 14th, 2016 - By Dan I Piraner

Nature Chemical Biology 13, 75 (2017). doi:10.1038/nchembio.2233 Authors: Dan I Piraner, Mohamad H Abedi, Brittany A Moser, Audrey Lee-Gosselin & Mikhail G…

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Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis

Posted on Nov 14th, 2016 - By Valerian E Kagan

Nature Chemical Biology 13, 81 (2017). doi:10.1038/nchembio.2238 Authors: Valerian E Kagan, Gaowei Mao, Feng Qu, Jose Pedro Friedmann Angeli, Sebastian Doll, Claudette St Croix, Haider Hussain Dar, Bing Liu, Vladimir A Tyurin, Vladimir B Ritov, Alexandr A Kapralov, Andrew A Amoscato, Jianfei Jiang, Tamil Anthonymuthu, Dariush Mohammadyani, Qin Yang, Bettina Proneth, Judith Klein-Seetharaman, Simon Watkins, Ivet Bahar, Joel Greenberger, Rama K Mallampalli, Brent R Stockwell, Yulia…

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Elucidation of gibberellin biosynthesis in bacteria reveals convergent evolution

Posted on Nov 14th, 2016 - By Ryan S Nett

Nature Chemical Biology 13, 69 (2017). doi:10.1038/nchembio.2232 Authors: Ryan S Nett, Mariana Montanares, Ariana Marcassa, Xuan Lu, Raimund Nagel, Trevor C Charles, Peter Hedden, Maria Cecilia Rojas & Reuben J…

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Ferroptosis: Oxidized PEs trigger death

Posted on Nov 14th, 2016 - By Katharina D'Herde

Nature Chemical Biology 13, 4 (2017). doi:10.1038/nchembio.2261 Authors: Katharina D'Herde & Dmitri V Krysko Ferroptosis is characterized by accumulation of lipid peroxidation products and lethal ROS, but the source and identity of lipid death signals that cause toxicity are poorly defined. New studies reveal that ACSL4 controls sensitivity to ferroptosis and that oxidized phosphatidylethanolamines are critical for ferroptosis…

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Identification of G-quadruplexes in long functional RNAs using 7-deazaguanine RNA

Posted on Nov 7th, 2016 - By Carika Weldon

Nature Chemical Biology 13, 18 (2017). doi:10.1038/nchembio.2228 Authors: Carika Weldon, Isabelle Behm-Ansmant, Laurence H Hurley, Glenn A Burley, Christiane Branlant, Ian C Eperon & Cyril Dominguez RNA G-quadruplex (G4) structures are thought to affect biological processes, including translation and pre-mRNA splicing, but it is not possible at present to demonstrate that they form naturally at specific sequences in long functional RNA molecules. We developed a new strategy,…

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DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis

Posted on Nov 7th, 2016 - By Marian C Okondo

Nature Chemical Biology 13, 46 (2017). doi:10.1038/nchembio.2229 Authors: Marian C Okondo, Darren C Johnson, Ramya Sridharan, Eun Bin Go, Ashley J Chui, Mitchell S Wang, Sarah E Poplawski, Wengen Wu, Yuxin Liu, Jack H Lai, David G Sanford, Michael O Arciprete, Todd R Golub, William W Bachovchin & Daniel A…

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Inhibition of RAS function through targeting an allosteric regulatory site

Posted on Nov 7th, 2016 - By Russell Spencer-Smith

Nature Chemical Biology 13, 62 (2017). doi:10.1038/nchembio.2231 Authors: Russell Spencer-Smith, Akiko Koide, Yong Zhou, Raphael R Eguchi, Fern Sha, Priyanka Gajwani, Dianicha Santana, Ankit Gupta, Miranda Jacobs, Erika Herrero-Garcia, Jacqueline Cobbert, Hugo Lavoie, Matthew Smith, Thanashan Rajakulendran, Evan Dowdell, Mustafa Nazir Okur, Irina Dementieva, Frank Sicheri, Marc Therrien, John F Hancock, Mitsuhiko Ikura, Shohei Koide & John P…

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Non-classical transpeptidases yield insight into new antibacterials

Posted on Nov 7th, 2016 - By Pankaj Kumar

Nature Chemical Biology 13, 54 (2017). doi:10.1038/nchembio.2237 Authors: Pankaj Kumar, Amit Kaushik, Evan P Lloyd, Shao-Gang Li, Rohini Mattoo, Nicole C Ammerman, Drew T Bell, Alexander L Perryman, Trevor A Zandi, Sean Ekins, Stephan L Ginell, Craig A Townsend, Joel S Freundlich & Gyanu…

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Genetic engineering: Chemical control for CRISPR editing

Posted on Nov 7th, 2016 - By Isaac B Hilton

Nature Chemical Biology 13, 2 (2017). doi:10.1038/nchembio.2243 Authors: Isaac B Hilton & Charles A Gersbach New approaches allow tight control over Cas9 activity using chemical induction. These studies expand the ability to rapidly induce and suppress Cas9-mediated nuclease activity and conditionally modulate the multiplex regulation of endogenous gene…

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Profiling drugs for rheumatoid arthritis that inhibit synovial fibroblast activation

Posted on Oct 31st, 2016 - By Douglas S Jones

Nature Chemical Biology 13, 38 (2017). doi:10.1038/nchembio.2211 Authors: Douglas S Jones, Anne P Jenney, Jennifer L Swantek, John M Burke, Douglas A Lauffenburger & Peter K…

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Structure of p300 in complex with acyl-CoA variants

Posted on Oct 31st, 2016 - By Zuzanna Kaczmarska

Nature Chemical Biology 13, 21 (2017). doi:10.1038/nchembio.2217 Authors: Zuzanna Kaczmarska, Esther Ortega, Afsaneh Goudarzi, He Huang, Sunjoo Kim, José A Márquez, Yingming Zhao, Saadi Khochbin & Daniel…

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A multi-step peptidolytic cascade for amino acid recovery in chloroplasts

Posted on Oct 31st, 2016 - By Pedro F Teixeira

Nature Chemical Biology 13, 15 (2017). doi:10.1038/nchembio.2227 Authors: Pedro F Teixeira, Beata Kmiec, Rui M M Branca, Monika W Murcha, Anna Byzia, Aneta Ivanova, James Whelan, Marcin Drag, Janne Lehtiö & Elzbieta Glaser Plastids (including chloroplasts) are subcellular sites for a plethora of proteolytic reactions, required in functions ranging from protein biogenesis to quality control. Here we show that peptides generated from pre-protein maturation within…

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Genome-wide genetic screening with chemically mutagenized haploid embryonic stem cells

Posted on Oct 31st, 2016 - By Josep V Forment

Nature Chemical Biology 13, 12 (2017). doi:10.1038/nchembio.2226 Authors: Josep V Forment, Mareike Herzog, Julia Coates, Tomasz Konopka, Bianca V Gapp, Sebastian M Nijman, David J Adams, Thomas M Keane & Stephen P Jackson In model organisms, classical genetic screening via random mutagenesis provides key insights into the molecular bases of genetic interactions, helping to define synthetic lethality, synthetic viability and drug-resistance mechanisms. The limited genetic…

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Multidimensional chemical control of CRISPR–Cas9

Posted on Oct 31st, 2016 - By Basudeb Maji

Nature Chemical Biology 13, 9 (2017). doi:10.1038/nchembio.2224 Authors: Basudeb Maji, Christopher L Moore, Bernd Zetsche, Sara E Volz, Feng Zhang, Matthew D Shoulders & Amit Choudhary Cas9-based technologies have transformed genome engineering and the interrogation of genomic functions, but methods to control such technologies across numerous dimensions—including dose, time, specificity, and mutually exclusive modulation of multiple genes—are still lacking. We…

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Dereplication of peptidic natural products through database search of mass spectra

Posted on Oct 31st, 2016 - By Hosein Mohimani

Nature Chemical Biology 13, 30 (2017). doi:10.1038/nchembio.2219 Authors: Hosein Mohimani, Alexey Gurevich, Alla Mikheenko, Neha Garg, Louis-Felix Nothias, Akihiro Ninomiya, Kentaro Takada, Pieter C Dorrestein & Pavel A…

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Potent and selective bivalent inhibitors of BET bromodomains

Posted on Oct 24th, 2016 - By Michael J Waring

Nature Chemical Biology 12, 1097 (2016). doi:10.1038/nchembio.2210 Authors: Michael J Waring, Huawei Chen, Alfred A Rabow, Graeme Walker, Romel Bobby, Scott Boiko, Rob H Bradbury, Rowena Callis, Edwin Clark, Ian Dale, Danette L Daniels, Austin Dulak, Liz Flavell, Geoff Holdgate, Thomas A Jowitt, Alexey Kikhney, Mark McAlister, Jacqui Méndez, Derek Ogg, Joe Patel, Philip Petteruti, Graeme R Robb, Matthew B Robers, Sakina Saif, Natalie Stratton, Dmitri I Svergun, Wenxian Wang,…

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Small-molecule factor D inhibitors targeting the alternative complement pathway

Posted on Oct 24th, 2016 - By Jürgen Maibaum

Nature Chemical Biology 12, 1105 (2016). doi:10.1038/nchembio.2208 Authors: Jürgen Maibaum, Sha-Mei Liao, Anna Vulpetti, Nils Ostermann, Stefan Randl, Simon Rüdisser, Edwige Lorthiois, Paul Erbel, Bernd Kinzel, Fabrice A Kolb, Samuel Barbieri, Julia Wagner, Corinne Durand, Kamal Fettis, Solene Dussauge, Nicola Hughes, Omar Delgado, Ulrich Hommel, Ty Gould, Aengus Mac Sweeney, Bernd Gerhartz, Frederic Cumin, Stefanie Flohr, Anna Schubart, Bruce Jaffee, Richard Harrison,…

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Selective recognition of histone crotonylation by double PHD fingers of MOZ and DPF2

Posted on Oct 24th, 2016 - By Xiaozhe Xiong

Nature Chemical Biology 12, 1111 (2016). doi:10.1038/nchembio.2218 Authors: Xiaozhe Xiong, Tatyana Panchenko, Shuang Yang, Shuai Zhao, Peiqiang Yan, Wenhao Zhang, Wei Xie, Yuanyuan Li, Yingming Zhao, C David Allis & Haitao…

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Design and characterization of bivalent BET inhibitors

Posted on Oct 24th, 2016 - By Minoru Tanaka

Nature Chemical Biology 12, 1089 (2016). doi:10.1038/nchembio.2209 Authors: Minoru Tanaka, Justin M Roberts, Hyuk-Soo Seo, Amanda Souza, Joshiawa Paulk, Thomas G Scott, Stephen L DeAngelo, Sirano Dhe-Paganon & James E…

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Synthetic biology: Cholera detectors

Posted on Oct 18th, 2016 - By Caitlin Deane

Nature Chemical Biology 12, 889 (2016). doi:10.1038/nchembio.2222 Author: Caitlin…

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Proteomics: Fishing for zinc

Posted on Oct 18th, 2016 - By Grant Miura

Nature Chemical Biology 12, 889 (2016). doi:10.1038/nchembio.2220 Author: Grant…

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Protein dynamics: Conformational footprints

Posted on Oct 18th, 2016 - By Buyong Ma

Nature Chemical Biology 12, 890 (2016). doi:10.1038/nchembio.2212 Authors: Buyong Ma & Ruth Nussinov 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…

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Insulin signaling: At a snail’s pace

Posted on Oct 18th, 2016 - By Stéphane Larochelle

Nature Chemical Biology 12, 889 (2016). doi:10.1038/nchembio.2221 Author: Stéphane…

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Long non-coding RNAs: Pulsating RNA motifs

Posted on Oct 18th, 2016 - By Terry L. Sheppard

Nature Chemical Biology 12, 889 (2016). doi:10.1038/nchembio.2223 Author: Terry L.…

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Antibiotics: New recipe for targeting resistance

Posted on Oct 18th, 2016 - By Balázs Papp

Nature Chemical Biology 12, 891 (2016). doi:10.1038/nchembio.2215 Authors: Balázs Papp & Viktória Lázár 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…

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Enzyme mechanisms: Sugary shears

Posted on Oct 18th, 2016 - By Ethan D Goddard-Borger

Nature Chemical Biology 12, 892 (2016). doi:10.1038/nchembio.2216 Author: Ethan D Goddard-Borger Proteolytic maturation of an important transcriptional regulator is performed by a glycosyltransferase. The reaction involves glycosylation of a glutamate residue and conversion of the γ-glycosyl ester product into an N-acyl pyroglutamate, which undergoes spontaneous hydrolysis to effect peptide backbone…

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Metabolic engineering: Biosensors get the green light

Posted on Oct 18th, 2016 - By Sarah K Hammer

Nature Chemical Biology 12, 894 (2016). doi:10.1038/nchembio.2214 Authors: Sarah K Hammer & José L Avalos 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…

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Structural basis of nonribosomal peptide macrocyclization in fungi

Posted on Oct 17th, 2016 - By Jinru Zhang

Nature Chemical Biology 12, 1001 (2016). doi:10.1038/nchembio.2202 Authors: Jinru Zhang, Nicholas Liu, Ralph A Cacho, Zhou Gong, Zhu Liu, Wenming Qin, Chun Tang, Yi Tang & Jiahai Zhou Nonribosomal peptide synthetases (NRPSs) in fungi biosynthesize important pharmaceutical compounds, including penicillin, cyclosporine and echinocandin. To understand the fungal strategy of forging the macrocyclic peptide linkage, we determined the crystal structures of the terminal…

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Discovery of MRSA active antibiotics using primary sequence from the human microbiome

Posted on Oct 17th, 2016 - By John Chu

Nature Chemical Biology 12, 1004 (2016). doi:10.1038/nchembio.2207 Authors: John Chu, Xavier Vila-Farres, Daigo Inoyama, Melinda Ternei, Louis J Cohen, Emma A Gordon, Boojala Vijay B Reddy, Zachary Charlop-Powers, Henry A Zebroski, Ricardo Gallardo-Macias, Mark Jaskowski, Shruthi Satish, Steven Park, David S Perlin, Joel S Freundlich & Sean F Brady Here we present a natural product discovery approach, whereby structures are bioinformatically predicted from primary sequence…

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Identification and characterization of PPARα ligands in the hippocampus

Posted on Oct 17th, 2016 - By Avik Roy

Nature Chemical Biology 12, 1075 (2016). doi:10.1038/nchembio.2204 Authors: Avik Roy, Madhuchhanda Kundu, Malabendu Jana, Rama K Mishra, Yeni Yung, Chi-Hao Luan, Frank J Gonzalez & Kalipada…

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A prevalent intraresidue hydrogen bond stabilizes proteins

Posted on Oct 17th, 2016 - By Robert W Newberry

Nature Chemical Biology 12, 1084 (2016). doi:10.1038/nchembio.2206 Authors: Robert W Newberry & Ronald T…

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Structural and conformational determinants of macrocycle cell permeability

Posted on Oct 17th, 2016 - By Björn Over

Nature Chemical Biology 12, 1065 (2016). doi:10.1038/nchembio.2203 Authors: Björn Over, Pär Matsson, Christian Tyrchan, Per Artursson, Bradley C Doak, Michael A Foley, Constanze Hilgendorf, Stephen E Johnston, Maurice D Lee, Richard J Lewis, Patrick McCarren, Giovanni Muncipinto, Ulf Norinder, Matthew W D Perry, Jeremy R Duvall & Jan…

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SF2312 is a natural phosphonate inhibitor of enolase

Posted on Oct 10th, 2016 - By Paul G Leonard

Nature Chemical Biology 12, 1053 (2016). doi:10.1038/nchembio.2195 Authors: Paul G Leonard, Nikunj Satani, David Maxwell, Yu-Hsi Lin, Naima Hammoudi, Zhenghong Peng, Federica Pisaneschi, Todd M Link, Gilbert R Lee, Duoli Sun, Basvoju A Bhanu Prasad, Maria Emilia Di Francesco, Barbara Czako, John M Asara, Y Alan Wang, William Bornmann, Ronald A DePinho & Florian L…

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Serine is a new target residue for endogenous ADP-ribosylation on histones

Posted on Oct 10th, 2016 - By Orsolya Leidecker

Nature Chemical Biology 12, 998 (2016). doi:10.1038/nchembio.2180 Authors: Orsolya Leidecker, Juan José Bonfiglio, Thomas Colby, Qi Zhang, Ilian Atanassov, Roko Zaja, Luca Palazzo, Anna Stockum, Ivan Ahel & Ivan Matic ADP-ribosylation (ADPr) is a biologically and clinically important post-translational modification, but little is known about the amino acids it targets on cellular proteins. Here we present a proteomic approach for direct in vivo identification and…

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A photoactivatable Cre–loxP recombination system for optogenetic genome engineering

Posted on Oct 10th, 2016 - By Fuun Kawano

Nature Chemical Biology 12, 1059 (2016). doi:10.1038/nchembio.2205 Authors: Fuun Kawano, Risako Okazaki, Masayuki Yazawa & Moritoshi…

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Competing charge transfer pathways at the photosystem II–electrode interface

Posted on Oct 10th, 2016 - By Jenny Z Zhang

Nature Chemical Biology 12, 1046 (2016). doi:10.1038/nchembio.2192 Authors: Jenny Z Zhang, Katarzyna P Sokol, Nicholas Paul, Elisabet Romero, Rienk van Grondelle & Erwin…

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Nuclear receptors control pro-viral and antiviral metabolic responses to hepatitis C virus infection

Posted on Oct 10th, 2016 - By Gahl Levy

Nature Chemical Biology 12, 1037 (2016). doi:10.1038/nchembio.2193 Authors: Gahl Levy, Naomi Habib, Maria Angela Guzzardi, Daniel Kitsberg, David Bomze, Elishai Ezra, Basak E Uygun, Korkut Uygun, Martin Trippler, Joerg F Schlaak, Oren Shibolet, Ella H Sklan, Merav Cohen, Joerg Timm, Nir Friedman & Yaakov…

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