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 SoĢnia Troeira Henriques and David J. Craik

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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

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ACS Chemical Biology
DOI: 10.1021/acschembio.6b00921

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

  • Posted in Nat Chem Biol, Publications
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Enzyme-catalyzed cationic epoxide rearrangements in quinolone alkaloid biosynthesis

January 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 Tang

  • Posted in Nat Chem Biol, Publications
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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

  • Posted in Nat Chem Biol, Publications
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RNA modification: Reading Sex-lethal

January 19th, 2017 by Grant Miura

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

Author: Grant Miura

Nitrogenase: A fuel-producing microbe

January 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 hydrocarbons.

Biosynthesis: Terrifically tailored peptides

January 19th, 2017 by Caitlin Deane

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

Author: Caitlin Deane