S-adenosyl-L-methionine-dependent methyltransferase (SAM-MTase) (SAM-MTase)

S-adenosyl-L-methionine-dependent methyltransferases (SAM-MTases) are a diverse superfamily of enzymes that facilitate the transfer of a methyl group from the universal donor, S-adenosyl-L-methionine (SAM or AdoMet), to a wide array of biological targets including DNA, RNA, proteins, and lipids (Petrossian & Clarke, 2011, Molecular & Cellular Proteomics). These enzymes are fundamental to epigenetic signaling, where they modify histones and DNA to regulate chromatin structure and gene expression (Greer & Shi, 2012, Nature Reviews Genetics). Beyond epigenetics, they are involved in the biosynthesis of neurotransmitters, the detoxification of xenobiotics, and the maturation of various RNA species (Schubert et al., 2003, BMC Genomics). In clinical contexts, the overexpression or mutation of specific SAM-MTases, such as EZH2 or DOT1L, is strongly associated with the progression of various cancers and hematological malignancies (Knutson et al., 2013, Nature Chemical Biology). Therapeutic strategies often involve small-molecule inhibitors that compete with SAM for the active site or block substrate binding, with several agents like tazemetostat already receiving regulatory approval (FDA, 2020). Despite their therapeutic potential, the high degree of structural homology within the SAM-binding domain across different family members presents a significant challenge for developing highly selective inhibitors without off-target effects (Spath et al., 2021, Communications Biology).

Other names

AdoMet-dependent methyltransferaseSAM-dependent methyltransferaseS-adenosylmethionine-dependent methyltransferaseMethyltransferase

Inhibition of the transfer of a methyl group from the universal methyl donor S-adenosyl-L-methionine (SAM or AdoMet) to specific substrates including DNA, RNA, proteins, and small molecules.