Protein N-myristoyltransferase (NMT)

Protein N-myristoyltransferase (NMT) is a ubiquitously expressed eukaryotic enzyme that catalyzes the irreversible covalent attachment of a myristoyl group (a 14-carbon saturated fatty acid, myristate) from myristoyl-CoA to the N-terminal glycine of substrate proteins, typically co-translationally after removal of the initiator methionine[1][2][5][6]. This lipid modification is crucial for membrane targeting, signal transduction, protein–protein interactions, and protein stability[4][5]. There are two major human isoforms, NMT1 and NMT2, both members of the GNAT superfamily, showing conserved CoA binding but differences in substrate specificity[1][2]. NMT is an essential enzyme, required for cell viability in all studied eukaryotes, and is a validated drug target in several infectious diseases (e.g., leishmaniasis, trypanosomiasis) and under investigation in cancer and viral infection[3][5][6][7]. Structural studies reveal a two-lobed enzyme that binds myristoyl-CoA and peptide substrates in a sequential manner, facilitating nucleophilic attack of the peptide’s glycine on the fatty acyl-CoA thioester[1][3][6]. Inhibitors of NMT disrupt membrane localization and function of key proteins, providing a mechanistic basis for therapeutic intervention in both infectious and neoplastic diseases[6][7]. Research attention is focused on developing selective inhibitors that effectively target pathogen NMT without harming essential host processes.

Other names

N-myristoyltransferaseGlycylpeptide N-tetradecanoyltransferaseNMT1 (isoform 1)NMT2 (isoform 2)

Inhibition of myristoylation of protein substrates by blocking NMT enzymatic activity; Disruption of protein membrane localization and signal transduction; Inhibition of pathogen survival and proliferation by targeting essential NMT function.