Molecular Enzymology of Phage T4 Dam DNA Methyltransferase

This review summarizes the results of a study of the molecular mechanisms of phage T4 DNA adenine methyltransferase (T4Dam) action. T4Dam [EC 2.1.1.72] catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (AdoMet) to N6 of the adenine located in the palindromic recognition site GATC. The subunit structure of T4Dam, substrate-binding properties, and kinetic parameters of methylation of a variety of native and modified oligonucleotide duplexes are considered. A kinetic scheme of the reaction was proposed, assuming that T4Dam is isomerized into a catalytically active form. The mechanisms of DNA-induced dimerization of T4Dam, flipping of the target base, reorientation of T4Dam on an asymmetrically methylated recognition site, the effector action of substrates, and processive methylation of extended DNA containing more than one specific site are discussed. The results obtained for T4Dam may provide a better understanding of the action mechanisms of other homologous enzymes including, first and foremost, those of the vast Dam family.