The Escherichia coli AlkA protein is a base excision repair glycosylase that 
removes a variety of alkylated bases from DNA. The 2.5 A crystal structure of 
AlkA complexed to DNA shows a large distortion in the bound DNA. The enzyme 
flips a 1-azaribose abasic nucleotide out of DNA and induces a 66 degrees bend 
in the DNA with a marked widening of the minor groove. The position of the 
1-azaribose in the enzyme active site suggests an S(N)1-type mechanism for the 
glycosylase reaction, in which the essential catalytic Asp238 provides direct 
assistance for base removal. Catalytic selectivity might result from the 
enhanced stacking of positively charged, alkylated bases against the aromatic 
side chain of Trp272 in conjunction with the relative ease of cleaving the 
weakened glycosylic bond of these modified nucleotides. The structure of the 
AlkA-DNA complex offers the first glimpse of a helix-hairpin-helix (HhH) 
glycosylase complexed to DNA. Modeling studies suggest that other HhH 
glycosylases can bind to DNA in a similar manner.