1VRL

MutY adenine glycosylase in complex with DNA and soaked adenine free base

Replaces:  1RRT

Summary for 1VRL

• Entry DOI: 10.2210/pdb1vrl/pdb
• Related: 1RRQ 1RRS
• Descriptor: 5'-D(*AP*AP*GP*AP*CP*(8OG)P*TP*GP*GP*AP*C)-3', 5'-D(*TP*GP*TP*CP*CP*AP*(HPD)P*GP*TP*CP*T)-3', MutY, ... (7 entities in total)
• Functional Keywords: dna repair, dna glycosylase, 8-oxoguanine, protein-dna complex, hydrolase-dna complex, hydrolase/dna
• Biological source: Geobacillus stearothermophilus
• Total number of polymer chains: 3
• Total formula weight: 49251.10

Authors

Fromme, J.C.,Banerjee, A.,Huang, S.J.,Verdine, G.L. (deposition date: 2005-03-08, release date: 2005-03-22, Last modification date: 2023-12-27)

Primary citation

Fromme, J.C.,Banerjee, A.,Huang, S.J.,Verdine, G.L.
Structural basis for removal of adenine mispaired with 8-oxoguanine by MutY adenine DNA glycosylase
Nature, 427:652-656, 2004

PubMed Abstract: The genomes of aerobic organisms suffer chronic oxidation of guanine to the genotoxic product 8-oxoguanine (oxoG). Replicative DNA polymerases misread oxoG residues and insert adenine instead of cytosine opposite the oxidized base. Both bases in the resulting A*oxoG mispair are mutagenic lesions, and both must undergo base-specific replacement to restore the original C*G pair. Doing so represents a formidable challenge to the DNA repair machinery, because adenine makes up roughly 25% of the bases in most genomes. The evolutionarily conserved enzyme adenine DNA glycosylase (called MutY in bacteria and hMYH in humans) initiates repair of A*oxoG to C*G by removing the inappropriately paired adenine base from the DNA backbone. A central issue concerning MutY function is the mechanism by which A*oxoG mispairs are targeted among the vast excess of A*T pairs. Here we report the use of disulphide crosslinking to obtain high-resolution crystal structures of MutY-DNA lesion-recognition complexes. These structures reveal the basis for recognizing both lesions in the A*oxoG pair and for catalysing removal of the adenine base.

PubMed: 14961129
DOI: 10.1038/nature02306

Experimental method

X-RAY DIFFRACTION (2.5 Å)