1EBM

CRYSTAL STRUCTURE OF THE HUMAN 8-OXOGUANINE GLYCOSYLASE (HOGG1) BOUND TO A SUBSTRATE OLIGONUCLEOTIDE

1EBM の概要

• エントリーDOI: 10.2210/pdb1ebm/pdb
• 分子名称: DNA (5'-D(*GP*CP*GP*TP*CP*CP*AP*(8OG)P*GP*TP*CP*TP*AP*CP*C)-3'), DNA (5'-D(*GP*GP*TP*AP*GP*AP*CP*CP*TP*GP*GP*AP*CP*GP*C)-3'), 8-OXOGUANINE DNA GLYCOSYLASE, ... (5 entities in total)
• 機能のキーワード: dna repair, dna glycosylase, protein/dna, lyase-dna complex, lyase/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: 44884.29

構造登録者

Bruner, S.D.,Norman, D.P.,Verdine, G.L. (登録日: 2000-01-24, 公開日: 2000-03-20, 最終更新日: 2024-02-07)

主引用文献

Bruner, S.D.,Norman, D.P.,Verdine, G.L.
Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA.
Nature, 403:859-866, 2000

PubMed Abstract: Spontaneous oxidation of guanine residues in DNA generates 8-oxoguanine (oxoG). By mispairing with adenine during replication, oxoG gives rise to a G x C --> T x A transversion, a frequent somatic mutation in human cancers. The dedicated repair pathway for oxoG centres on 8-oxoguanine DNA glycosylase (hOGG1), an enzyme that recognizes oxoG x C base pairs, catalysing expulsion of the oxoG and cleavage of the DNA backbone. Here we report the X-ray structure of the catalytic core of hOGG1 bound to oxoG x C-containing DNA at 2.1 A resolution. The structure reveals the mechanistic basis for the recognition and catalytic excision of DNA damage by hOGG1 and by other members of the enzyme superfamily to which it belongs. The structure also provides a rationale for the biochemical effects of inactivating mutations and polymorphisms in hOGG1. One known mutation, R154H, converts hOGG1 to a promutator by relaxing the specificity of the enzyme for the base opposite oxoG.

PubMed: 10706276
DOI: 10.1038/35002510

実験手法

X-RAY DIFFRACTION (2.1 Å)