Nmyristoyltransferaasin

N-myristoyltransferase (NMT) is a conserved transferase enzyme that catalyzes the covalent attachment of a myristoyl group (a 14‑carbon saturated fatty acid) to the N‑terminus of target proteins through an amide bond. The reaction consumes myristoyl‑CoA as the donor substrate and requires an N‑terminal glycine on the acceptor protein. NMT is essential for the proper localization, stability, and function of many signaling proteins, including Src family kinases, Ras, and various proteins involved in signal transduction and membrane trafficking. In eukaryotes, two isoforms are typically encoded, NMT1 and NMT2, which display overlapping but distinct substrate specificities and subcellular distributions.

The catalytic core of NMT consists of a Rossmann‑like α/β fold that binds both the fatty acyl‑CoA and the protein substrate. Structural studies have revealed an active‑site pocket lined with hydrophobic residues that accommodate the myristate moiety, and a conserved Lys/Arg network that stabilizes the transition state. NMT belongs to the transferase family (EC 2.3.1.86) and shares mechanistic features with other acyl‑transferases, yet its substrate recognition is highly specific.

Abnormal N‑myristoylation is implicated in several diseases. Over‑expression of NMT enhances oncogenic signaling in cancers such as breast, lung, and colon, and inhibitors of NMT are being explored as potential anticancer therapeutics. Moreover, mutations affecting NMT activity can disrupt membrane protein sorting and have been linked to neurodegenerative disorders. Because of its central role in protein maturation and signaling, NMT remains a valuable target for drug discovery and a critical component of cellular regulation.