Reaction pathway of UDG. A stepwise mechanism has been established involving a discrete oxacarbenium ion intermediate that is stabilized by electrostatic interactions with active site residues and the phosphodiester groups of the DNA. Two catalytic groups are indicated in the figure: His268, which serves as a hydrogen bond donor to stabilize the developing negative charge on uracil O2 in the dissociative transition state, and Asp145, which stabilizes the cationic sugar of the intermediate. The structure of 1-aza-deoxyribose (1-aza-dR), which is proposed to mimic the sugar conformation in the second transition state involving water addition, is also shown.