Interactions of human 8-oxoguanine DNA glycosylase with single- and double-stranded DNAs

The interaction of human 8-oxoguanine (8-oxoG) DNA glycosylase (hOGG1) with single- and double-stranded oligodeoxyribonucleotides (ODNs) was studied by a method of stepwise increase in ligand complexity. ODNs were shown to act as competitive inhibitors with respect to the substrate of the reaction catalyzed by hOGG1. K-1 was estimated for various homo- and hetero-ODNs. All nucleotides covered by the enzyme globule proved to additively interact with hOGG1. An increase in the ODN size n by one nucleotide or base pair in d(pN)(n) and their duplexes monotonically increased their affinity for hOGG1 by a factor of 1.4-1.5 until n = 10, mostly due to weak nonspecific additive contacts between hOGG1 and the sugar-phosphate backbone. Weak nonspecific additive interactions contributed about five orders of magnitude to the total affinity of hOGG1 for specific DNA (K-d similar to 10(-5) M). Specific 8-oxoG increased the affinity of DNA for the enzyme by three orders of magnitude (K-d similar to 10(-8) M). The main features of the recognition of specific DNA by hOGG1 were analyzed.