S-adenosylmethionine-dependent methyltransferase (SAM-MTase) (SAM-MTase)

S-adenosylmethionine-dependent methyltransferases (SAM-MTases) constitute a vast and diverse superfamily of enzymes that catalyze the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to a wide array of biological targets, including DNA, RNA, proteins, lipids, and small molecules (UniProt Family: SAM-dependent methyltransferase). These enzymes are fundamental to epigenetic regulation, where they modify histones and DNA to control gene expression patterns without altering the underlying genetic code (PMID: 30242151). Beyond epigenetics, they are involved in the biosynthesis of neurotransmitters, the detoxification of xenobiotics, and the maturation of various RNA species. Dysregulation or mutation of specific SAM-MTases, such as EZH2 or DNMT1, is frequently implicated in the pathogenesis of various cancers, leading to the silencing of tumor suppressor genes or the activation of oncogenic pathways (PMID: 26111143). Consequently, this class of enzymes has become a significant focus for drug development, with several small-molecule inhibitors like Tazemetostat currently approved or in clinical trials for treating hematological malignancies and solid tumors (FDA, 2020). The therapeutic potential of targeting these enzymes extends to neurodegenerative and metabolic diseases, though achieving selectivity remains a primary challenge due to the structural conservation of the SAM-binding pocket across the superfamily.

Other names

SAM-dependent methyltransferaseAdoMet-dependent methyltransferaseS-adenosyl-L-methionine-dependent methyltransferaseMethyltransferase

Inhibition of the transfer of a methyl group from the universal methyl donor S-adenosyl-L-methionine (SAM) to specific substrates such as DNA, RNA, or proteins, often through competitive binding at the SAM-binding site or the substrate-binding pocket (PMID: 26111143).