1YQR

Catalytically inactive human 8-oxoguanine glycosylase crosslinked to oxoG containing DNA

1YQR の概要

• エントリーDOI: 10.2210/pdb1yqr/pdb
• 関連するPDBエントリー: 1EBM 1YQK 1YQL 1YQM
• 分子名称: 5'-D(P*GP*GP*TP*AP*GP*AP*CP*CP*TP*GP*GP*AP*CP*G)-3', 5'-D(P*CP*GP*TP*CP*CP*AP*(8OG)P*GP*TP*CP*TP*AP*CP*C)-3', N-glycosylase/DNA lyase, ... (5 entities in total)
• 機能のキーワード: disulfide crosslinking, crosslinking validation, hydrolase-dna complex, hydrolase/dna
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus, nucleoplasm . Isoform 1A: Nucleus. Isoform 2A: Mitochondrion: O15527
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 44629.42

構造登録者

Banerjee, A.,Yang, W.,Karplus, M.,Verdine, G.L. (登録日: 2005-02-02, 公開日: 2005-04-05, 最終更新日: 2024-02-14)

主引用文献

Banerjee, A.,Yang, W.,Karplus, M.,Verdine, G.L.
Structure of a repair enzyme interrogating undamaged DNA elucidates recognition of damaged DNA.
Nature, 434:612-618, 2005

PubMed Abstract: How DNA repair proteins distinguish between the rare sites of damage and the vast expanse of normal DNA is poorly understood. Recognizing the mutagenic lesion 8-oxoguanine (oxoG) represents an especially formidable challenge, because this oxidized nucleobase differs by only two atoms from its normal counterpart, guanine (G). Here we report the use of a covalent trapping strategy to capture a human oxoG repair protein, 8-oxoguanine DNA glycosylase I (hOGG1), in the act of interrogating normal DNA. The X-ray structure of the trapped complex features a target G nucleobase extruded from the DNA helix but denied insertion into the lesion recognition pocket of the enzyme. Free energy difference calculations show that both attractive and repulsive interactions have an important role in the preferential binding of oxoG compared with G to the active site. The structure reveals a remarkably effective gate-keeping strategy for lesion discrimination and suggests a mechanism for oxoG insertion into the hOGG1 active site.

PubMed: 15800616
DOI: 10.1038/nature03458

実験手法

X-RAY DIFFRACTION (2.43 Å)