Depurination of N7-methylguanine by DNA glycosylase AlkD is dependent on the DNA backbone.

Rubinson EH, Christov PP, Eichman BF
Biochemistry. 2013 52 (42): 7363-5

PMID: 24090276 · PMCID: PMC3852881 · DOI:10.1021/bi401195r

DNA glycosylase AlkD excises N7-methylguanine (7mG) by a unique but unknown mechanism, in which the damaged nucleotide is positioned away from the protein and the phosphate backbone is distorted. Here, we show by methylphosphonate substitution that a phosphate proximal to the lesion has a significant effect on the rate enhancement of 7mG depurination by the enzyme. Thus, instead of a conventional mechanism whereby protein side chains participate in N-glycosidic bond cleavage, AlkD remodels the DNA into an active site composed exclusively of DNA functional groups that provide the necessary chemistry to catalyze depurination.

MeSH Terms (11)

Catalysis Catalytic Domain Crystallography, X-Ray DNA DNA Glycosylases DNA Repair Guanine Humans Models, Molecular Protein Conformation Purines

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