Methyltransferases and Radical SAM enzymes

Methyltransferases and Radical SAM enzymes are two expansive superfamilies of enzymes that primarily utilize S-adenosyl-L-methionine (SAM) to facilitate diverse biochemical transformations. Methyltransferases (MTases) are responsible for transferring a methyl group to substrates such as DNA, histones, and small molecules, playing a fundamental role in epigenetic signaling and metabolic homeostasis (UniProt, 2024). Radical SAM enzymes utilize a [4Fe-4S] cluster to generate a highly reactive 5'-deoxyadenosyl radical, allowing them to perform challenging reactions like C-H bond activation and the synthesis of complex vitamins and antibiotics (Frey et al., 2008). These enzymes are significant therapeutic targets; for example, DNA methyltransferase inhibitors like azacitidine are used in treating myelodysplastic syndromes, while histone methyltransferase inhibitors like tazemetostat are used in oncology (NIH, 2023). Furthermore, catechol-O-methyltransferase (COMT) inhibitors are employed in Parkinson's disease management to prolong the effect of levodopa (StatPearls, 2023). Radical SAM enzymes are also investigated as targets for novel antimicrobials due to their involvement in bacterial resistance and essential metabolic pathways (PubMed, 2022).

Other names

MethylasesSAM-dependent methyltransferasesRadical S-adenosylmethionine enzymesRSM enzymesS-adenosyl-L-methionine-dependent methyltransferasesRadical SAM methyltransferases

Inhibition of methyl group transfer to DNA or histones; inhibition of catecholamine degradation; disruption of radical-mediated catalysis in bacterial pathways.