UNIVERSAL CATALYTIC DOMAIN-STRUCTURE OF ADOMET-DEPENDENT METHYLTRANSFERASES

The DNA methyltransferases, M.HhaI and M.TaqI, and catechol O-methyltr ansferase (COMT) catalyze the transfer of a methyl group from the cofa ctor S-adenosyl-L-methionine (AdoMet) to carbon-5 of cytosine, to nitr ogen-6 of adenine, and to a hydroxyl group of catechol, respectively; The catalytic domains of the bilobal proteins, M.HhaI and M.TaqI, and the entire single domain of COMT have similar folding with an alpha/be ta structure containing a mixed central beta-sheet. The functional res idues are located in equivalent regions at the carboxyl ends of the pa rallel beta-strands. The cofactor binding sites are almost identical a nd the essential catalytic amino acids coincide. The comparable protei n folding and the existence of equivalent amino acids in similar secon dary and tertiary positions indicate that many (if not all) AdoMet-dep endent methyltransferases have a common catalytic domain structure. Th is permits tertiary structure prediction of other DNA, RNA, protein, a nd small-molecule AdoMet-dependent methyltransferases from their amino acid sequences.