8DWE

Adenine glycosylase MutY variant E43Q in complex with DNA containing d(8-oxo-G) paired with substrate purine

8DWE の概要

• エントリーDOI: 10.2210/pdb8dwe/pdb
• 関連するPDBエントリー: 8DWD 8DWE 8DWF
• 分子名称: Adenine DNA glycosylase, DNA (5'-D(*AP*AP*GP*AP*CP*(8OG)P*TP*GP*GP*AP*C)-3'), DNA (5'-D(*TP*GP*TP*CP*CP*AP*(PRN)P*GP*TP*CP*T)-3'), ... (8 entities in total)
• 機能のキーワード: protein-dna complex, dna repair, base excision repair, hydrolase, 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: 6
• 化学式量合計: 98242.08

構造登録者

Russelburg, L.P.,Demir, M.,David, S.S.,Horvath, M.P. (登録日: 2022-08-01, 公開日: 2023-08-09, 最終更新日: 2026-06-03)

主引用文献

Russelburg, L.P.,Demir, M.,Cedeno, K.,David, S.S.,Horvath, M.P.
Structural Basis for Nucleobase Activation by the Adenine DNA Glycosylase MutY.
Biorxiv, 2026

PubMed Abstract: MutY excises adenine (A) from 8-oxo-guanine:adenine (OG:A) lesions in DNA to initiate base excision repair (BER) and thereby prevent mutations. A catalytic Glu, found at position 43 in the enzyme from ( MutY), protonates the nucleobase at N to labilize the N-glycosidic bond. The resulting oxocarbenium ion transition state is stabilized by a covalent DNA-enzyme intermediate and resolved by nucleophilic attack to yield the -anomer abasic AP site product. The retaining SN1 mechanism for MutY posits deprotonation of the nucleophile by the catalytic Glu. Here we tested kinetic and structural consequences of Glu replacement and found that E43Q and E43S substitution variants were severely impaired, retained measurable activity, but engage the substrate nucleobase in an conformation, rotated by 180 ° from the conformation seen in previous substrate complexes. The enzyme-generated AP product is observed in its -anomer configuration for these Glu-replacement variants. Comparison with inverting adenine glycosylases that act on RNA or nucleosides shows that MutY's mechanism is uniquely reliant on one catalytic residue for both leaving group and nucleophile activation, a situation that may serve to ensure only rare adenines paired with OG are excised.

PubMed: 41648512
DOI: 10.64898/2026.01.22.701053

実験手法

X-RAY DIFFRACTION (2.2 Å)