DNA Glycosylase - Biochemical Mechanism

Biochemical Mechanism

The first crystal structure of a DNA glycosylase was obtained for E. coli Nth. This structure revealed that the enzyme flips the damaged base out of the double helix into an active site pocket in order to excise it. Other glycosylases have since been found to follow the same general paradigm, including human UNG pictured below. To cleave the N-glycosidic bond, monofunctional glycosylases use an activated water molecule to attack carbon 1 of the substrate. Bifunctional glycosylases, instead, use an amine residue as a nucleophile to attack the same carbon, going through a Schiff base intermediate.