1EBM

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

Summary for 1EBM

• Entry DOI: 10.2210/pdb1ebm/pdb
• Descriptor: 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)
• Functional Keywords: dna repair, dna glycosylase, protein/dna, lyase-dna complex, lyase/dna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus, nucleoplasm. Isoform 1A: Nucleus. Isoform 2A: Mitochondrion: O15527
• Total number of polymer chains: 3
• Total formula weight: 44884.29

Authors

Bruner, S.D.,Norman, D.P.,Verdine, G.L. (deposition date: 2000-01-24, release date: 2000-03-20, Last modification date: 2024-02-07)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.1 Å)