Glycylpeptide N-tetradecanoyltransferase (N-myristoyltransferase) (NMT)

Glycylpeptide N-tetradecanoyltransferase, commonly known as N-myristoyltransferase (NMT), is a critical enzyme that catalyzes the covalent attachment of myristic acid to the N-terminal glycine of various proteins. This modification, N-myristoylation, is essential for the membrane anchoring and functional activation of over 100 proteins involved in signal transduction, such as Src-family kinases and G-proteins (UniProt: P30419, O60551). In humans, NMT exists as two isoforms, NMT1 and NMT2; notably, some cancers exhibit NMT2 deficiency, creating a synthetic lethal vulnerability to NMT1 inhibitors (Beauchamp et al., 2020). Beyond oncology, NMT is a validated target for infectious diseases, as it is required for the life cycle of pathogens like Plasmodium falciparum and various viruses, including rhinovirus and HIV (Wright et al., 2014; Mousnier et al., 2018). Therapeutic development focuses on small-molecule inhibitors that block the peptide or myristoyl-CoA binding sites to prevent the modification of downstream effectors. However, the broad range of human substrates presents a significant challenge for achieving a therapeutic window without inducing systemic toxicity.

Other names

N-myristoyltransferaseNMT1NMT2Myristoyl-CoA:protein N-myristoyltransferaseN-terminal myristoyltransferase

Competitive inhibition of the N-myristoyltransferase enzyme, preventing the covalent attachment of myristate to the N-terminal glycine of substrate proteins, thereby disrupting their membrane localization and biological function.