Structure-based sequence alignment of three AdoMet-dependent DNA methyltransferases

M.HhaI, M.TaqI and COMT are DNA methyltransferases (MTases) which catalyze the transfer of a methyl group from the cofactor AdoMet to C5 of cytosine, to N6 of adenine and to a hydroxyl group of catechol, respectively. The larger catalytic domains of the bilobal proteins, M.HhaI and M.TaqI, and the entire single domain of COMT have an alpha/beta structure containing a mixed central beta-sheet. These domains have very similar folding. By allowing appropriate 'insertions' or 'deletions' in the backbones of the three structures, it was possible to find more conserved motifs in M.TaqI and COMT. The similarity in protein folding and the equivalence of amino-acid sequences revealed by the structural alignment indicate that many AdoMet-dependent MTases may share a common catalytic domain structure.