3-DIMENSIONAL STRUCTURE OF THE ADENINE-SPECIFIC DNA METHYLTRANSFERASE M-CENTER-DOT-TAQ-I IN COMPLEX WITH THE COFACTOR S-ADENOSYLMETHIONINE

The Thermus aquaticus DNA methyltransferase M.Taq I (EC 2.1.1.72) methylates N-6 of adenine in the specific double-helical DNA sequence TCGA by transfer of -CH3 from the cofactor S-adenosyl-L-methionine. The x-ray crystal structure at 2.4-Angstrom resolution of this enzyme in complex with S-adenosylmethionine shows alpha/beta folding of the polypeptide into two domains of about equal size. They are arranged in the form of a C with a wide deft suitable to accommodate the DNA substrate. The N-terminal domain is dominated by a nine-stranded beta-sheet; it contains the two observed segments typical for N-methyltransferases which form a pocket for cofactor binding. The C-terminal domain is formed by four small beta-sheets and alpha helices. The three-dimensional folding of M.Taq I is similar to that of the cytosine-specific Hha I methyltransferase, where the large beta-sheet in the N-terminal domain contains all conserved segments and the enzymatically functional parts, and the smaller C-terminal domain is less structured.