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Meeting Report

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.


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News and Views

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 & 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.


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Brief Communication

Acetylation serves as a protective group in noscapine biosynthesis in opium poppy pp104 - 106

Thu-Thuy T Dang, Xue Chen & Peter J Facchini

doi:10.1038/nchembio.1717

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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.


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Articles

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, Shivendra Kishore, Panagiota Tsikrika, André P Gerber, Mihaela Zavolan & Jonathan Hall

doi:10.1038/nchembio.1713

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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.

See also: News and Views by Grimson


De novo biosynthesis of terminal alkyne-labeled natural products pp115 - 120

Xuejun Zhu, Joyce Liu & Wenjun Zhang

doi:10.1038/nchembio.1718

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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.

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 & Bernhard Hauer

doi:10.1038/nchembio.1719

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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, Motoki Murai, Takuya Kaji, Takefumi Kuranaga, Kenji Hamase, Takashi Katsu, Jie Su, Tatsuo Adachi, Ryuji Uchida, Hiroshi Tomoda, Maki Yamada, Manabu Souma, Hiroki Kurihara, Masayuki Inoue & Kazuhisa Sekimizu

doi:10.1038/nchembio.1710

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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.


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, Jean-Philippe Pin & Philippe Rondard

doi:10.1038/nchembio.1711

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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, Brian M Sanchez, Jay M Wendling, Rodney W Morgan, Tom D Aicher, Laura L Carter, Peter L Toogood & Gary D Glick

doi:10.1038/nchembio.1714

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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 & Manajit Hayer-Hartl

doi:10.1038/nchembio.1715

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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, Péter Nagy, Frauke Gräter & Tobias P Dick

doi:10.1038/nchembio.1720

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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, Thomas D Bird, Amy R Howell & Benjamin F Cravatt

doi:10.1038/nchembio.1721

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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.

See also: News and Views by Kim


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Errata

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


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Corrigenda

Corrigendum: Combating neurodegenerative disease with chemical probes and model systems p172

Priyanka Narayan, Sepehr Ehsani & 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, Donald Rau & Alex Evilevitch

doi:10.1038/nchembio0215-172d


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