Human alkyladenine glycosylase (AAG) and Escherichia coli 3-methyladenine 
glycosylase (AlkA) are base excision repair glycosylases that recognize and 
excise a variety of alkylated bases from DNA. The crystal structures of these 
enzymes have provided insight into their substrate specificity and mechanisms of 
catalysis. Both enzymes utilize DNA bending and base-flipping mechanisms to 
expose and bind substrate bases. Crystal structures of AAG complexed to DNA 
suggest that the enzyme selects substrate bases through a combination of 
hydrogen bonding and the steric constraints of the active site, and that the 
enzyme activates a water molecule for an in-line backside attack of the 
N-glycosylic bond. In contrast to AAG, the structure of the AlkA-DNA complex 
suggests that AlkA substrate recognition and catalytic specificity are 
intimately integrated in a S(N)1 type mechanism in which the catalytic Asp238 
directly promotes the release of modified bases.