K. Goedecke et al., Structure of the N6-adenine DNA methyltransferase M center dot Taql in complex with DNA and a cofactor analog, NAT ST BIOL, 8(2), 2001, pp. 121-125
The 2.0 Angstrom crystal structure of the N6-adenine DNA methyltransferase
M-TaqI in complex with specific DNA and a nonreactive cofactor analog revea
ls a previously unrecognized stabilization of the extrahelical target base.
To catalyze the transfer of the methyl group from the cofactor S-adenosyl-
L-methionine to the C-amino group of adenine within the double-stranded DNA
sequence 5'-TCGA-3', the target nucleoside is rotated out of the DNA helix
. Stabilization of the extrahelical conformation is achieved by DNA compres
sion perpendicular to the DNA helix axis at the target base pair position a
nd relocation of the partner base thymine in an interstrand re-stacked posi
tion, where it would sterically overlap with an innerhelical target adenine
. The extrahelical target adenine Is specifically recognized in the active
site, and the 6-amino group of adenine donates two hydrogen bonds to Asn 10
5 and Pro 106, which both belong to the conserved catalytic motif IV of N6-
adenine DNA methyltransferases, These hydrogen bonds appear to increase the
partial negative charge of the N6 atom of adenine and activate it for dire
ct nucleophilic attack on the methyl group of the cofactor.