Glycylpeptide N-tetradecanoyltransferase (NMT) (NMT)

Glycylpeptide N-tetradecanoyltransferase, commonly known as N-myristoyltransferase (NMT), is a ubiquitous eukaryotic enzyme that catalyzes the N-myristoylation of proteins, a critical post-translational modification [1, 5]. This process involves the covalent attachment of a 14-carbon saturated fatty acid, myristate, to the N-terminal glycine residue of a variety of cellular and viral proteins [7, 10]. Myristoylation is essential for the proper membrane anchoring, stability, and biological activity of numerous signaling proteins, including Src family kinases, G-proteins, and ARF GTPases [1, 2, 7]. In humans, two distinct isoforms, NMT1 and NMT2, carry out these functions with overlapping but specific substrate preferences and tissue distributions [3, 4]. NMT has emerged as a significant therapeutic target in oncology, as its overexpression is linked to the progression of various cancers, such as colorectal, breast, and lung cancer, as well as acute myeloid leukemia (AML) [1, 11]. Furthermore, NMT is a validated target for treating infectious diseases, including viral infections (e.g., HIV, rhinovirus) and parasitic diseases (e.g., malaria, leishmaniasis), because these pathogens rely on NMT-mediated myristoylation for their replication and assembly [1, 9, 10]. Therapeutic strategies involve the development of small molecule inhibitors, such as zelenirstat, which disrupt the myristoylation of key oncogenic or viral proteins, leading to protein degradation and apoptosis [4, 11].

Other names

N-myristoyltransferaseMyristoyl-CoA:protein N-myristoyltransferasePeptide N-myristoyltransferaseNMT1NMT2Glycylpeptide N-tetradecanoyltransferase 1Glycylpeptide N-tetradecanoyltransferase 2

Inhibition of N-myristoyltransferase activity, which prevents the N-myristoylation of substrate proteins (such as Src family kinases or viral capsid proteins), leading to loss of membrane localization, increased protein degradation, induction of endoplasmic reticulum stress, and apoptosis [1, 4, 11].