Trapping and structural elucidation of a very advanced intermediate in the lesion-extrusion pathway of hOGG1.

ABSTRACT: Here we present the first structure of a very advanced intermediate in the lesion-extrusion pathway of a DNA glycosylase, human 8-oxoguanine DNA glycosylase (hOGG1), and a substrate DNA containing a mutagenic lesion, 8-oxoguanine (oxoG). The structure was obtained by irradiation and flash-freezing of a disulfide-cross-linked (DXLed) complex of hOgg1 bound to DNA containing a novel photocaged derivative of oxoG. The X-ray structure reveals that, upon irradiation, the oxoG lesion has transited from the exosite to the active site pocket, but has not undergone cleavage by the enzyme. Furthermore, all but one of the specificity-determining interactions between the lesion and the enzyme are unformed in the flashed complex (FC), because active site functionality and elements of the DNA backbone a

SUBMITTER: Lee S 

PROVIDER: S-EPMC2878488 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature