Nmyristoyltransferases

N-myristoyltransferases (NMTs) are enzymes that catalyze the transfer of the 14-carbon fatty acid myristate from myristoyl-CoA to the N-terminal glycine of substrate proteins, forming an amide linkage. The modification is typically co-translational, occurring after the initiator methionine is removed to reveal an N-terminal glycine.

In humans, two main isoforms exist: NMT1 and NMT2, encoded by separate genes and sharing a conserved catalytic domain. Most substrates are proteins that present an exposed N-terminal glycine, though there is some flexibility in sequence context.

N-myristoylation influences membrane association, subcellular localization, and protein–protein interactions, and it is essential for many signaling proteins. Because of its widespread role, NMT activity is important for viability in several organisms and for the virulence of certain pathogens.

NMTs are conserved across eukaryotes and are present in many pathogens, making them attractive drug targets. NMT inhibitors are under investigation as antiparasitic and anticancer agents; several lead compounds block myristoyl-CoA binding or catalytic turnover.

Biochemically, NMT has a bilobal catalytic core that binds both substrates. Structural and biochemical studies support the mechanism of amide bond formation. Researchers study NMT using enzymatic assays, structural biology, and metabolic labeling methods.