methyltransferase

Methyltransferases are a broad class of enzymes that transfer a methyl group from a donor, most commonly S-adenosylmethionine (SAM), to an acceptor molecule. The reaction produces S-adenosylhomocysteine (SAH) and a methylated substrate. Methylation modulates the function, localization, or interaction of the substrate and is a key mechanism in epigenetic regulation, metabolism, and signaling.

Substrates include DNA, RNA, proteins, lipids, and small molecules. DNA methyltransferases add methyl groups to cytosine residues (5-methylcytosine) in eukaryotes and bacteria. RNA methyltransferases install methyl marks such as N6-methyladenosine in mRNA. Protein methyltransferases modify lysine or arginine residues on histones and other proteins, influencing chromatin structure and protein activity. Lipid methyltransferases modify phospholipids and other lipids; small-molecule methyltransferases act on compounds such as catechols, neurotransmitters, and drugs.

Most methyltransferases use SAM as the methyl donor; the transfer is typically a nucleophilic substitution at the methyl carbon. Many enzymes belong to conserved structural families and often employ a Rossmann-like fold; in eukaryotes, various classes include DNA cytosine-5 methyltransferases, protein lysine/arginine methyltransferases, and histone methyltransferases such as those bearing SET domains.

Key human enzymes include DNA methyltransferases DNMT1, DNMT3A, and DNMT3B; RNA methyltransferase complexes such as METTL3–METTL14; histone lysine methyltransferases (e.g., EZH2, SET-domain containing enzymes); arginine methyltransferases (PRMTs); and the catechol O-methyltransferase (COMT).

Abnormal methylation is linked to development, cancer, and metabolic disorders. Inhibitors targeting methyltransferases are used in research and therapeutics, and methylation patterns serve as biomarkers of cellular state.