Molecular basis for discriminating between normal and damaged bases by thehuman alkyladenine glycosylase, AAG

The human 3-methyladenine DNA glycosylase [alkyladenine DNA glycosylase (AA G)] catalyzes the first step of base excision repair by cleaving damaged ba ses from DNA. Unlike other DNA glycosylases that are specific for a particu lar type of damaged base, AAG excises a chemically diverse selection of sub strate bases damaged by alkylation or deamination. The 2.1-Angstrom, crysta l structure of AAG complexed to DNA containing 1,N-6-ethenoadenine suggests how modified bases can be distinguished from normal DNA bases in the enzym e active site. Mutational analyses of residues contacting the alkylated bas e in the crystal structures suggest that the shape of the damaged base, its hydrogen-bonding characteristics, and its aromaticity all contribute to th e selective recognition of damage by AAG.