4YOQ

Crystal Structure of MutY bound to its anti-substrate

4YOQ の概要

• エントリーDOI: 10.2210/pdb4yoq/pdb
• 関連するPDBエントリー: 4YPH 4YPR
• 分子名称: A/G-specific adenine glycosylase, DNA (5'-D(*AP*AP*GP*AP*CP*(8OG)P*TP*GP*GP*AP*C)-3'), DNA (5'-D(*T*GP*TP*CP*CP*AP*CP*GP*TP*CP*T)-3'), ... (7 entities in total)
• 機能のキーワード: 8-oxoguanine, base-excision repair, anti-substrate, hydrolase-dna complex, hydrolase/dna
• 由来する生物種: Geobacillus stearothermophilus; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 49289.06

構造登録者

Wang, L.,Lee, S.,Verdine, G.L. (登録日: 2015-03-11, 公開日: 2015-05-27, 最終更新日: 2023-09-27)

主引用文献

Wang, L.,Lee, S.J.,Verdine, G.L.
Structural Basis for Avoidance of Promutagenic DNA Repair by MutY Adenine DNA Glycosylase.
J.Biol.Chem., 290:17096-17105, 2015

PubMed Abstract: The highly mutagenic A:oxoG (8-oxoguanine) base pair in DNA most frequently arises by aberrant replication of the primary oxidative lesion C:oxoG. This lesion is particularly insidious because neither of its constituent nucleobases faithfully transmit genetic information from the original C:G base pair. Repair of A:oxoG is initiated by adenine DNA glycosylase, which catalyzes hydrolytic cleavage of the aberrant A nucleobase from the DNA backbone. These enzymes, MutY in bacteria and MUTYH in humans, scrupulously avoid processing of C:oxoG because cleavage of the C residue in C:oxoG would actually promote mutagenic conversion to A:oxoG. Here we analyze the structural basis for rejection of C:oxoG by MutY, using a synthetic crystallography approach to capture the enzyme in the process of inspecting the C:oxoG anti-substrate, with which it ordinarily binds only fleetingly. We find that MutY uses two distinct strategies to avoid presentation of C to the enzyme active site. Firstly, MutY possesses an exo-site that serves as a decoy for C, and secondly, repulsive forces with a key active site residue prevent stable insertion of C into the nucleobase recognition pocket within the enzyme active site.

PubMed: 25995449
DOI: 10.1074/jbc.M115.657866

実験手法

X-RAY DIFFRACTION (2.21 Å)