Tuesday, January 20, 2015

Nature Chemical Biology Contents: February 2015, Volume 11 No 2 pp 91 - 172

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Nature Chemical Biology

TABLE OF CONTENTS

February 2015 Volume 11, Issue 2

Meeting Report
Research Highlights
News and Views
Brief Communication
Articles
Errata
Corrigenda

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Meeting Report

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Chemical biologists rush to San Francisco for the ICBS   pp91 - 95
Evan W Miller
doi:10.1038/nchembio.1742
An international group of chemical biologists convened in San Francisco to present the latest scientific findings, discuss future directions and be inspired by research at the interface of chemistry and biology. This report on the third annual conference of the International Chemical Biology Society provides a brief overview of the meeting and its scientific program.

Research Highlights

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RNA metabolism: With or without U | Metabolism: First aid for flavin | Alzheimer's disease: Bound with Aβ | Fat development: BATting the WAT | Stem cells: Food for renewal | Drug discovery: Death by sodium


News and Views

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Biosynthesis: A terminal triple bond toolbox   pp98 - 99
Victoria S Haritos
doi:10.1038/nchembio.1731
Terminal triple bonds feature in natural products, but their biosynthesis is little known. Now a terminal acetylenase has been characterized for substrate specificity for the first time, and an application to 'bio-click' chemistry has been shown by incorporation of the moiety into natural product scaffolds.

See also: Article by Zhu et al.

Phospholipids: A neuroinflammation emerging target   pp99 - 100
Hee-Yong Kim
doi:10.1038/nchembio.1740
Lysophosphatidylserines (lyso-PSs) are an emerging class of signaling lipids implicated in human inflammatory and autoimmune diseases. A newly discovered phosphatidylserine-specific lipase, ABHD16A, together with the recently described lyso-PS lipase ABHD12 shed light on the in vivo regulation of lyso-PS, providing a potential enzymatic target for modulating neuroinflammatory responses.

See also: Article by Kamat et al.

Noncoding RNA: Linking microRNAs to their targets   pp100 - 101
Andrew Grimson
doi:10.1038/nchembio.1741
The reliable identification of microRNA (miRNA) targets remains an elusive goal. A new technique, using specially modified synthetic miRNAs to directly capture bound RNAs, brings us closer.

See also: Article by Imig et al.

Membrane enzymes: Transformers at the interface   pp102 - 103
Florian Brodhun and Kai Tittmann
doi:10.1038/nchembio.1738
Recent studies on two enzyme classes operating at the membrane interface showcase an unanticipated degree of structural plasticity involving domain swapping and marked secondary structure reshuffling. This structural variability in topology is key to functional diversification and catalytic prowess.

See also: Article by Golczak et al. | Brief Communication by Giganti et al.

Chemical Biology
JOBS of the week
PhD Position in Chemical Biology
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Brief Communication

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Acetylation serves as a protective group in noscapine biosynthesis in opium poppy   pp104 - 106
Thu-Thuy T Dang, Xue Chen and Peter J Facchini
doi:10.1038/nchembio.1717



Characterization of four enzymes involved in biosynthesis of the plant metabolite and anticancer agent noscapine completes this pathway and identifies an unusual acetyl protecting group strategy that defines the order of enzymatic steps.
Chemical compounds

Articles

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miR-CLIP capture of a miRNA targetome uncovers a lincRNA H19–miR-106a interaction   pp107 - 114
Jochen Imig, Andreas Brunschweiger, Anneke Brümmer, Boris Guennewig, Nitish Mittal et al.
doi:10.1038/nchembio.1713



Validation of the cellular targets of microRNAs remains an ongoing priority. miR-CLIP, a new method based on psoralen crosslinking, immunoprecipitation and biotin affinity pulldowns, was applied to determine the miR-106a targetome, which included the H19 lncRNA.
Chemical compounds
See also: News and Views by Grimson

De novo biosynthesis of terminal alkyne-labeled natural products   pp115 - 120
Xuejun Zhu, Joyce Liu and Wenjun Zhang
doi:10.1038/nchembio.1718



Genetic evidence suggested jamABC from the jamaicamide biosynthetic pathway were responsible for the synthesis of the terminal alkyne functional group. Biochemical studies now confirm this activity and demonstrate the insertion of alkynes into two unrelated natural products.
Chemical compounds
See also: News and Views by Haritos

Squalene hopene cyclases are protonases for stereoselective Brønsted acid catalysis   pp121 - 126
Stephan C Hammer, Antonija Marjanovic, Jörg M Dominicus, Bettina M Nestl and Bernhard Hauer
doi:10.1038/nchembio.1719



Biocatalysis can take advantage of an enzyme's inherent reactivity regardless of its physiological role, as shown for a terpene cyclase turned Brønsted acid catalyst after its active site pocket was mutated while the activated aspartic acid was retained.

Lysocin E is a new antibiotic that targets menaquinone in the bacterial membrane   pp127 - 133
Hiroshi Hamamoto, Makoto Urai, Kenichi Ishii, Jyunichiro Yasukawa, Atmika Paudel et al.
doi:10.1038/nchembio.1710



A family of cyclic lipopeptide natural products named lysocins was isolated from a soil bacteria sample and was found to exhibit antimicrobial actions. Genetic and biochemical evidence showed that lysocin E targets bacterial menaquinone.
Chemical compounds

Major ligand-induced rearrangement of the heptahelical domain interface in a GPCR dimer   pp134 - 140
Li Xue, Xavier Rovira, Pauline Scholler, Han Zhao, Jianfeng Liu et al.
doi:10.1038/nchembio.1711



Disulfide trapping and FRET studies define an agonist-induced conformational change in mGlu2 from inactive symmetric dimers with an interface at transmembrane domains (TMs) 4 and 5 to an active state with TM6s serving as the dimer interface.

Sterol metabolism controls TH17 differentiation by generating endogenous RORγ agonists   pp141 - 147
Xiao Hu, Yahong Wang, Ling-Yang Hao, Xikui Liu, Chuck A Lesch et al.
doi:10.1038/nchembio.1714



Desmosterol acts as an endogenous RORγ agonist during differentiation of CD4+ T cells into the TH17 lineage, where there is increased cholesterol biosynthesis and uptake and decreased cholesterol metabolism and efflux that cause accumulation of desmosterol.

Opposing effects of folding and assembly chaperones on evolvability of Rubisco   pp148 - 155
Paulo Durão, Harald Aigner, Péter Nagy, Oliver Mueller-Cajar, F Ulrich Hartl et al.
doi:10.1038/nchembio.1715



Although nonspecific chaperones such as GroEL can increase evolvability by helping slightly destabilized mutants, a dedicated assembly chaperone decreases evolvability of the CO2 fixation enzyme Rubisco, providing insights into Rubisco's poor catalytic power.

A proton relay enhances H2O2 sensitivity of GAPDH to facilitate metabolic adaptation   pp156 - 163
David Peralta, Agnieszka K Bronowska, Bruce Morgan, Éva Dóka, Koen Van Laer et al.
doi:10.1038/nchembio.1720



The metabolic enzyme GAPDH exhibits oxidative inactivation in response to H2O2. A proton relay system was identified that enhances H2O2 sensitivity of GAPDH distinct from its catalytic activity, which ensures viability under oxidative stress.

Immunomodulatory lysophosphatidylserines are regulated by ABHD16A and ABHD12 interplay   pp164 - 171
Siddhesh S Kamat, Kaddy Camara, William H Parsons, Dong-Hui Chen, Melissa M Dix et al.
doi:10.1038/nchembio.1721



ABHD16A is identified as a major enzyme catalyzing production of lyso-PS from phosphatidylserine (PS). A new ABHD16A inhibitor and knockout mice show a dynamic interplay occurring during inflammation between ABHD16A and disease-linked ABHD12, an enzyme that degrades lyso-PS.
Chemical compounds
See also: News and Views by Kim

Errata

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Erratum: Microbiomes: Gut persuasions   p172
Mirella Bucci
doi:10.1038/nchembio0215-172a

Erratum: Protein dynamics: Tuning disorder propensity in p53   p172
Richard W Kriwacki
doi:10.1038/nchembio0215-172b

Corrigenda

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Corrigendum: Combating neurodegenerative disease with chemical probes and model systems   p172
Priyanka Narayan, Sepehr Ehsani and Susan Lindquist
doi:10.1038/nchembio0215-172c

Corrigendum: Solid-to-fluid DNA transition inside HSV-1 capsid close to the temperature of infection   p172
Udom Sae-Ueng, Dong Li, Xiaobing Zuo, Jamie B Huffman, Fred L Homa et al.
doi:10.1038/nchembio0215-172d

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