Nature Chemical Biology Contents: December 2016, Volume 12 No 12 pp 989 - 1118

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Advertisement Nature Outlook: Precision Medicine Health care that is tailored on the basis of an individual's genes, lifestyle or environment, is not a modern concept. But advances in genetics and the growing availability of health data for researchers and physicians promise to make this new era of medicine more personalized than ever before. Access the Outlook free online for six months Sponsored by: Illumina, Inc.    TABLE OF CONTENTS December 2016 Volume 12, Issue 12 Research Highlights News and Views Brief Communications Articles Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement npj Science of Food is a new open access journal that is now open for submissions. The journal aims to understand how processing influences biological functions of food in hope to support and nucleate maturation of these areas of research. Sign up for article e-alerts   Research Highlights Top RNA structure: Know when to fold 'em | Immunology: T cells get L-ARGed | Epigenomics: Massive ATAC | Protein synthesis: Breaking down the NSA1 News and Views Top Photosynthesis: Short circuit at the chlorophyll   pp990 - 991 Marc M Nowaczyk and Nicolas Plumere doi:10.1038/nchembio.2240 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 modification. See also: Article by Zhang et al. Drug discovery: Doubling down on BET inhibition   pp991 - 992 Dafydd Owen doi:10.1038/nchembio.2242 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 date. See also: Article by Tanaka et al. | Article by Waring et al. Nuclear receptors: PPARα ligands make memories   pp993 - 994 Thomas P Burris doi:10.1038/nchembio.2241 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 plasticity. See also: Article by Roy 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 Cbr1 is a Dph3 reductase required for the tRNA wobble uridine modification   pp995 - 997 Zhewang Lin, Min Dong, Yugang Zhang, Eunyoung Alisa Lee and Hening Lin doi:10.1038/nchembio.2190 A proteomic approach in Saccharomyces cerevisiae identifies cytochrome b reductase (Cbr1) as an NADH-dependent electron donor for diphthamide biosynthesis 3 (Dph3), a protein that serves as an electron source for diphthamide biosynthesis and tRNA modification. Serine is a new target residue for endogenous ADP-ribosylation on histones   pp998 - 1000 Orsolya Leidecker, Juan Jose Bonfiglio, Thomas Colby, Qi Zhang, Ilian Atanassov et al. doi:10.1038/nchembio.2180 ADP-ribosylation is a post-translational protein modification that regulates numerous cellular pathways. An approach involving histone purification, partial filter-aided digestion and ETD mass spectrometry reveals that serine residues in histone proteins are ADP-ribosylated. Structural basis of nonribosomal peptide macrocyclization in fungi   pp1001 - 1003 Jinru Zhang, Nicholas Liu, Ralph A Cacho, Zhou Gong, Zhu Liu et al. doi:10.1038/nchembio.2202 Unlike their bacterial counterparts, fungal nonribosomal peptide synthetases utilize a terminal condensation-like (CT) domain to form macrocycles, details of which are illuminated by structures of a CT domain and neighboring thiolation domain. Discovery of MRSA active antibiotics using primary sequence from the human microbiome   pp1004 - 1006 John Chu, Xavier Vila-Farres, Daigo Inoyama, Melinda Ternei, Louis J Cohen et al. doi:10.1038/nchembio.2207 The synthetic bioinformatic natural products (syn-BNPs) approach identifies putative natural products that are validated directly by independent synthesis. Its application led to the identification of humimycins, non-ribosomal peptides that have antimicrobial activity in mice. 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 Polyketide and nonribosomal peptide retro-biosynthesis and global gene cluster matching   pp1007 - 1014 Chris A Dejong, Gregory M Chen, Haoxin Li, Chad W Johnston, Mclean R Edwards et al. doi:10.1038/nchembio.2188 Two programs, GRAPE and GARLIC, work together to first predict biosynthetic gene clusters responsible for the production of polyketides and nonribosomal peptides, then link sequenced gene clusters to known and unknown natural products. Functional mining of transporters using synthetic selections   pp1015 - 1022 Hans J Genee, Anne P Bali, Soren D Petersen, Solvej Siedler, Mads T Bonde et al. doi:10.1038/nchembio.2189 Functional annotation of bacterial thiamine transporters via a generalizable synthetic biology approach using riboswitches identifies a novel family of thiamine-uptake systems from prokaryotic metagenomes, including PnuT, as well as two novel xanthine importers. Oligosaccharyltransferase inhibition induces senescence in RTK-driven tumor cells   pp1023 - 1030 Cecilia Lopez-Sambrooks, Shiteshu Shrimal, Carol Khodier, Daniel P Flaherty, Natalie Rinis et al. doi:10.1038/nchembio.2194 A high-throughput screen identifies NGI-1 as an inhibitor of oligosaccharyltransferase, preventing transfer of N-linked glycans to proteins. NGI-1 blocked EGFR signaling in non-small-cell lung cancer cell lines and promoted cell-cycle arrest and senescence. Chemical compounds Enzymatic hydrolysis by transition-metal-dependent nucleophilic aromatic substitution   pp1031 - 1036 Sibel Kalyoncu, David P Heaner Jr, Zohre Kurt, Casey M Bethel, Chiamaka U Ukachukwu et al. doi:10.1038/nchembio.2191 5-nitroanthranilic acid aminohydrolase catalyzes the first step in biodegradation of a nitroaromatic compound via a nucleophilic aromatic substitution mechanism with an unusual substrate-assisted metal loading step. Chemical compounds Nuclear receptors control pro-viral and antiviral metabolic responses to hepatitis C virus infection   pp1037 - 1045 Gahl Levy, Naomi Habib, Maria Angela Guzzardi, Daniel Kitsberg, David Bomze et al. doi:10.1038/nchembio.2193 A metabolomics analysis finds that host glycolysis, fatty acid oxidation, the urea cycle, cholesterol biosynthesis and oxidative phosphorylation are modified by hepatitis C virus infection. These effects are mediated through nuclear receptor transcription factors HNF4α, PPARα and FXR. Competing charge transfer pathways at the photosystem II-electrode interface   pp1046 - 1052 Jenny Z Zhang, Katarzyna P Sokol, Nicholas Paul, Elisabet Romero, Rienk van Grondelle et al. doi:10.1038/nchembio.2192 When coupled to electrodes, the photosystem II complex can participate in a photo-induced oxygen reduction mechanism via chlorophyll a pigments that competes against the desired water-oxidation charge transfer pathway. See also: News and Views by Nowaczyk & Plumere SF2312 is a natural phosphonate inhibitor of enolase   pp1053 - 1058 Paul G Leonard, Nikunj Satani, David Maxwell, Yu-Hsi Lin, Naima Hammoudi et al. doi:10.1038/nchembio.2195 SF2312, a phosphonate antibiotic, directly binds and inhibits the activity of the glycolytic enzyme enolase and is selectively toxic to ENO1-deleted glioma cells through inhibition of glycolysis and depletion of ATP. Chemical compounds A photoactivatable Cre-loxP recombination system for optogenetic genome engineering   pp1059 - 1064 Fuun Kawano, Risako Okazaki, Masayuki Yazawa and Moritoshi Sato doi:10.1038/nchembio.2205 The Cre-loxP recombination system is a classical tool for targeted genetic engineering. Blue-light-induced dimerization of a split Cre system enables efficient light-controlled DNA integration at loxP sites within cells and in living mouse tissues. Structural and conformational determinants of macrocycle cell permeability   pp1065 - 1074 Bjorn Over, Par Matsson, Christian Tyrchan, Per Artursson, Bradley C Doak et al. doi:10.1038/nchembio.2203 Detailed computational and structural analysis of a large data set of non-peptidic macrocycles revealed particular functional groups, substituents and molecular properties that are critical for dictating cellular permeability. Chemical compounds Identification and characterization of PPARα ligands in the hippocampus   pp1075 - 1083 Avik Roy, Madhuchhanda Kundu, Malabendu Jana, Rama K Mishra, Yeni Yung et al. doi:10.1038/nchembio.2204 Three endogenous ligands of the nuclear receptor PPARα—hydroxydimethylbutyrate, hexadecanamide, and octadecenamide—are potentially responsible for noncanonical activity of PPARα in synaptic function and hippocampal plasticity. See also: News and Views by Burris A prevalent intraresidue hydrogen bond stabilizes proteins   pp1084 - 1088 Robert W Newberry and Ronald T Raines doi:10.1038/nchembio.2206 Within polypeptides, C5 hydrogen bonds form between the amide proton and carbonyl oxygen of the same residue. This intraresidue interaction stabilizes β-sheets in particular and is widespread throughout structurally characterized proteins. Chemical compounds Design and characterization of bivalent BET inhibitors   pp1089 - 1096 Minoru Tanaka, Justin M Roberts, Hyuk-Soo Seo, Amanda Souza, Joshiawa Paulk et al. doi:10.1038/nchembio.2209 Targeting the acetyllysine 'reader' activity of BET family transcriptional coactivators has emerged as an anticancer modality. A new class of dimeric JQ1 derivatives displays enhanced potency for bivalent targeting of tandem bromodomains in BET proteins. Chemical compounds See also: News and Views by Owen Potent and selective bivalent inhibitors of BET bromodomains   pp1097 - 1104 Michael J Waring, Huawei Chen, Alfred A Rabow, Graeme Walker, Romel Bobby et al. doi:10.1038/nchembio.2210 Structural insights demonstrating small-molecule-mediated dimerization of BRD4 bromodomains led to the development of biBET, a compound that potently inhibits BRD4-acetyl-lysine interactions by bivalent binding to tandem bromodomains. Chemical compounds See also: News and Views by Owen Small-molecule factor D inhibitors targeting the alternative complement pathway   pp1105 - 1110 Jurgen Maibaum, Sha-Mei Liao, Anna Vulpetti, Nils Ostermann, Stefan Randl et al. doi:10.1038/nchembio.2208 A fragment-based design approach identifies reversible inhibitors targeting human protease complement factor D (FD), which is required for amplification of complement C3 signaling. FD inhibitors act as systemic regulators of complement activation in vivo. Chemical compounds Selective recognition of histone crotonylation by double PHD fingers of MOZ and DPF2   pp1111 - 1118 Xiaozhe Xiong, Tatyana Panchenko, Shuang Yang, Shuai Zhao, Peiqiang Yan et al. doi:10.1038/nchembio.2218 Structural and biophysical analysis of the histone acetyltransferase MOZ double PHD finger (DPF) domain reveal that DPF exhibits strong binding preference for crotonylated Lys14 in histone H3 (H3K14) and are co-localized in cells. 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