Methyltransferases

Methyltransferases represent a group of enzymes, most which, over 95%, use S-adenosyl-. l-methionine (AdoMet) as a methyl donor. The basic methyl transfer reaction is the catalytic attack of a nucleophile (carbon, oxygen, nitrogen, or sulfur) on a methyl group to form methylated derivatives of proteins, lipids, polysaccharides, nucleic acids, and various small molecules. Methyl conjugation is an important pathway in the metabolism of many drugs and xenobiotic compounds, as well as endogenous neurotransmitters and hormones. Methylation is also fundamental for the regulation of gene transcription. AdoMet-dependent methyltransferase enzymes are an example of convergent evolution, a series of enzymes with very different overall structures but with similar properties at the active site, which enables catalysis of the methyl transfer reaction (Schluckebier et al., 1995; Schubert et al., 2003). There are five structurally distinct families of AdoMet-dependent methyltransferases, each family representing a series of enzymes with structurally similar active sites and, between methyltransferase classes, different structures with similar functions (Schubert et al., 2003). The Enzyme Commission (EC) has allocated numbers to over 250 methyltransferases: the N-methylation of pyridine, documented in the late 19th century, was the first methyl conjugation reaction to be described (His, 1887; Weinshilboum et al., 1999), and tellurite methyltransferase (EC 2.1.1.265) will almost certainly not be the last.