The EED protein–protein interaction inhibitor A-395 inactivates the PRC2 complex

January 30th, 2017 by Yupeng He

Nature Chemical Biology 13, 389 (2017). doi:10.1038/nchembio.2306

Authors: Yupeng He, Sujatha Selvaraju, Michael L Curtin, Clarissa G Jakob, Haizhong Zhu, Kenneth M Comess, Bailin Shaw, Juliana The, Evelyne Lima-Fernandes, Magdalena M Szewczyk, Dong Cheng, Kelly L Klinge, Huan-Qiu Li, Marina Pliushchev, Mikkel A Algire, David Maag, Jun Guo, Justin Dietrich, Sanjay C Panchal, Andrew M Petros, Ramzi F Sweis, Maricel Torrent, Lance J Bigelow, Guillermo Senisterra, Fengling Li, Steven Kennedy, Qin Wu, Donald J Osterling, David J Lindley, Wenqing Gao, Scott Galasinski, Dalia Barsyte-Lovejoy, Masoud Vedadi, Fritz G Buchanan, Cheryl H Arrowsmith, Gary G Chiang, Chaohong Sun & William N Pappano

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An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED

January 30th, 2017 by Wei Qi

Nature Chemical Biology 13, 381 (2017). doi:10.1038/nchembio.2304

Authors: Wei Qi, Kehao Zhao, Justin Gu, Ying Huang, Youzhen Wang, Hailong Zhang, Man Zhang, Jeff Zhang, Zhengtian Yu, Ling Li, Lin Teng, Shannon Chuai, Chao Zhang, Mengxi Zhao, HoMan Chan, Zijun Chen, Douglas Fang, Qi Fei, Leying Feng, Lijian Feng, Yuan Gao, Hui Ge, Xinjian Ge, Guobin Li, Andreas Lingel, Ying Lin, Yueqin Liu, Fangjun Luo, Minlong Shi, Long Wang, Zhaofu Wang, Yanyan Yu, Jue Zeng, Chenhui Zeng, Lijun Zhang, Qiong Zhang, Shaolian Zhou, Counde Oyang, Peter Atadja & En Li

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Chromatin biology: Breaking into the PRC2 cage

January 30th, 2017 by Daniel Holoch

Nature Chemical Biology 13, 345 (2017). doi:10.1038/nchembio.2313

Authors: Daniel Holoch & Raphaël Margueron

New small-molecule inhibitors of the histone methyltransferase PRC2 interfere with the allosteric activation of enzymatic activity. These compounds are effective against PRC2-dependent tumors that are resistant to catalytic inhibitors and provide important new tools for altering chromatin regulation.

HTS-compatible FRET-based conformational sensors clarify membrane receptor activation

January 30th, 2017 by Pauline Scholler

Nature Chemical Biology 13, 372 (2017). doi:10.1038/nchembio.2286

Authors: Pauline Scholler, David Moreno-Delgado, Nathalie Lecat-Guillet, Etienne Doumazane, Carine Monnier, Fabienne Charrier-Savournin, Ludovic Fabre, Cédric Chouvet, Stéphanie Soldevila, Laurent Lamarque, Geoffrey Donsimoni, Thomas Roux, Jurriaan M Zwier, Eric Trinquet, Philippe Rondard & Jean-Philippe Pin

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Structural Basis for the Lesion-scanning Mechanism of the Bacterial MutY DNA Glycosylase [Enzymology]

January 27th, 2017 by Lan Wang, Srinivas Chakravarthy, Gregory L Verdine

The highly mutagenic A:oxoG (8-oxoguanine) base-pair is generated mainly by misreplication of the C:oxoG base-pair, the oxidation product of the C:G base-pair. A:oxoG base-pair is particularly insidious because neither base in it carries faithful information to direct the repair of the other. The bacterial MutY (MUTYH in humans) adenine DNA glycosylase is able to initiate the repair of A:oxoG by selectively cleaving the A base from the A:oxoG base-pair. The difference between faithful repair and wreaking mutagenic havoc on the genome lies in the accurate discrimination between two structurally similar base-pairs: A:oxoG and A:T. Here we present two crystal structures of the MutY N-terminal domain in complex with either undamaged DNA or DNA containing an intrahelical lesion. These structures have captured for the first time, a DNA glycosylase scanning the genome for a damaged base in the very first stage of lesion-recognition and the base-extrusion pathway. The mode of interaction observed here has suggested a common lesion-scanning mechanism across the entire helix-hairpin-helix superfamily to which MutY belongs. In addition, small-angle X-ray scattering (SAXS) studies together with accompanying biochemical assays have suggested a possible role played by the C-terminal oxoG-recognition domain of MutY in lesion-scanning.

Cyclotide Structure and Function: The Role of Membrane Binding and Permeation

January 27th, 2017 by Sónia Troeira Henriques and David J. Craik

TOC Graphic

Biochemistry
DOI: 10.1021/acs.biochem.6b01212

Differential Ability of Five DNA Glycosylases to Recognize and Repair Damage on Nucleosomal DNA

January 23rd, 2017 by Eric D. Olmon and Sarah Delaney

TOC Graphic

ACS Chemical Biology
DOI: 10.1021/acschembio.6b00921

Redox regulation: Taking AKTion on HNEs

January 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 zebrafish.

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

January 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, Vijayaratnam Santhakumar, Alberto Martin, Judd C Rice, Gary G Chiang, Masoud Vedadi, Dalia Barsyte-Lovejoy & William N Pappano

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

January 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 Aye

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