ABSTRACT
S-adenosyl-L-methionine (AdoMet)-dependent methyltransferases (MTases) are involved in diverse cellularfunctions. These enzymes show little sequence conservation but have a conserved structural fold. The DNAMTases have characteristic motifs that are involved in AdoMet binding, DNA target recognition and catalysis.Motif III of these MTases have a highly conserved acidic residue, often an aspartate, whose functionalsignificance is not clear. Here, we report a mutational study of the residue in the b family MTase of the Type IIIrestriction-modification enzyme EcoP15I. Replacement of this residue by alanine affects its methylationactivity. We propose that this residue contributes to the affinity of the enzyme for AdoMet. Analysis of thestructures of DNA, RNA and protein MTases reveal that the acidic residue is conserved in all of them, andinteracts with N6 of the adenine moiety of AdoMet. Interestingly, in the SET-domain protein lysine MTases,which have a fold different from other AdoMet-dependent MTases, N6 of the adenine moiety is hydrogenbonded to the main chain carbonyl group of the histidine residue of the highly conserved motif III. Our studyreveals the evolutionary conservation of a carbonyl group in DNA, RNA and protein AdoMet-dependentMTases for specific interaction by hydrogen bond with AdoMet, despite the lack of overall sequenceconservation