Protein methyltransferase (PMT) (PMT)

Protein methyltransferases (PMTs) are a major class of enzymes responsible for the post-translational modification of proteins by transferring a methyl group from S-adenosyl-L-methionine (SAM) to specific lysine or arginine residues [UniProt, Nature Reviews Drug Discovery]. These enzymes play a critical role in epigenetic regulation by modifying histone tails, thereby altering chromatin structure and governing gene expression patterns [Nature Reviews Genetics]. Beyond histones, PMTs also methylate various non-histone proteins involved in signal transduction, DNA damage repair, and RNA processing [Nature Reviews Drug Discovery, Chemical Reviews]. In many cancers, PMTs are frequently overexpressed, mutated, or translocated, leading to aberrant gene silencing or activation that promotes tumor growth and survival [Trends in Cancer, Expert Opinion on Therapeutic Targets]. As a result, PMTs have become high-priority targets for drug development, with several inhibitors targeting specific members like EZH2 and PRMT5 currently in clinical use or advanced development [Chemical Reviews, FDA]. Therapeutic strategies often involve small molecules that compete with the SAM cofactor or the protein substrate to block enzymatic activity [Chemical Reviews]. While targeting PMTs offers significant therapeutic potential, challenges include achieving isoform selectivity and managing systemic toxicities related to global epigenetic changes [Chemical Reviews]. Clinical success has been demonstrated with the approval of EZH2 inhibitors for specific lymphomas and sarcomas [FDA].

Other names

Protein-methyltransferaseS-adenosylmethionine-dependent protein methyltransferaseHistone methyltransferase (HMT)

Inhibition of the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to lysine or arginine residues on substrate proteins, often through SAM-competitive or substrate-competitive binding [Chemical Reviews].