Interactions along the reaction coordinate of UNG. E, free UNG (PDB entry 1AKZ); EI, UNG complex with nonspecific DNA showing a partially flipped base (PDB entry 2OXM); ES, UNG complex with substrate analogue DNA with uracil fully flipped into the active site (PDB entry 1EMH); ES‡, UNG complex with DNA containing a 1-azadeoxyribose glycosyl cation mimic and uracil (PDB entry 1Q3F); EP, UNG product complex with abasic DNA and uracil (PDB entry 1EMJ). Distances indicate potentially important interactions made by the +1 and +2 phosphates, His 148, and the catalytic water in each step along the reaction coordinate.