2XHI: Separation-of-function Mutants Unravel The Dual Reaction Mode Of Human 8-oxoguanine Dna Glycosylase

Citation:
Abstract
7,8-Dihydro-8-oxoguanine (8oxoG) is a major mutagenic base lesion formed when reactive oxygen species react with guanine in DNA. The human 8oxoG DNA glycosylase (hOgg1) recognizes and initiates repair of 8oxoG. hOgg1 is acknowledged as a bifunctional DNA glycosylase catalyzing removal of the damaged base followed by cleavage of the backbone of the intermediate abasic DNA (AP lyase/beta-elimination). When acting on 8oxoG-containing DNA, these two steps in the hOgg1 catalysis are considered coupled, with Lys249 implicated as a key residue. However, several lines of evidence point to a concurrent and independent monofunctional hydrolysis of the N-glycosylic bond being the in vivo relevant reaction mode of hOgg1. Here, we present biochemical and structural evidence for the monofunctional mode of hOgg1 by design of separation-of-function mutants. Asp268 is identified as the catalytic residue, while Lys249 appears critical for the specific recognition and final alignment of 8oxoG during the hydrolysis reaction.
PDB ID: 2XHIDownload
MMDB ID: 88169
PDB Deposition Date: 2010/6/16
Updated in MMDB: 2014/09
Experimental Method:
x-ray diffraction
Resolution: 1.55  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 2XHI: trimeric; determined by author and by software (PISA)
Molecular Components in 2XHI
Label Count Molecule
Protein (1 molecule)
1
N-glycosylase/dna Lyase(Gene symbol: OGG1)
Molecule annotation
Nucleotides(2 molecules)
1
5'-d(*gp*gp*tp*ap*gp*ap*cp*cp*tp*gp*gp*ap*cp*gp*c)-3'
Molecule annotation
1
5'-d(*gp*cp*gp*tp*cp*cp*ap*(8og)p*gp*tp*cp*tp*ap*cp*c)-3'
Molecule annotation
Chemicals (2 molecules)
1
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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