5DFJ

Human APE1 E96Q/D210N mismatch substrate complex

5DFJ の概要

• エントリーDOI: 10.2210/pdb5dfj/pdb
• 関連するPDBエントリー: 5DFF 5DFH 5DFI
• 分子名称: DNA-(apurinic or apyrimidinic site) lyase, DNA (5'-D(*GP*CP*TP*GP*AP*TP*GP*CP*GP*TP*(3DR)P*CP*GP*AP*CP*GP*GP*AP*TP*CP*C)-3'), DNA (5'-D(*GP*GP*AP*TP*CP*CP*GP*TP*CP*GP*GP*GP*CP*GP*CP*AP*TP*CP*AP*GP*C)-3'), ... (6 entities in total)
• 機能のキーワード: hydrolase, lyase/dna, lyase-dna complex
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus. DNA-(apurinic or apyrimidinic site) lyase, mitochondrial: Mitochondrion: P27695
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 75577.11

構造登録者

Freudenthal, B.D.,Wilson, S.H. (登録日: 2015-08-26, 公開日: 2015-10-14, 最終更新日: 2024-03-13)

主引用文献

Freudenthal, B.D.,Beard, W.A.,Cuneo, M.J.,Dyrkheeva, N.S.,Wilson, S.H.
Capturing snapshots of APE1 processing DNA damage.
Nat.Struct.Mol.Biol., 22:924-931, 2015

PubMed Abstract: DNA apurinic-apyrimidinic (AP) sites are prevalent noncoding threats to genomic stability and are processed by AP endonuclease 1 (APE1). APE1 incises the AP-site phosphodiester backbone, generating a DNA-repair intermediate that is potentially cytotoxic. The molecular events of the incision reaction remain elusive, owing in part to limited structural information. We report multiple high-resolution human APE1-DNA structures that divulge new features of the APE1 reaction, including the metal-binding site, the nucleophile and the arginine clamps that mediate product release. We also report APE1-DNA structures with a T-G mismatch 5' to the AP site, representing a clustered lesion occurring in methylated CpG dinucleotides. These structures reveal that APE1 molds the T-G mismatch into a unique Watson-Crick-like geometry that distorts the active site, thus reducing incision. These snapshots provide mechanistic clarity for APE1 while affording a rational framework to manipulate biological responses to DNA damage.

PubMed: 26458045
DOI: 10.1038/nsmb.3105

実験手法

X-RAY DIFFRACTION (1.85 Å)