NMT1

NMT1, or N-myristoyltransferase 1, is a cytosolic enzyme that catalyzes the transfer of a myristoyl group from myristoyl-CoA to the amino group of an N-terminal glycine on substrate proteins. This co-translational lipid modification helps anchor proteins to membranes and modulates protein–protein interactions and signaling.

In humans, NMT1 is one of two paralogous enzymes, along with NMT2. The NMT1 and NMT2 genes encode enzymes with overlapping but not identical substrate preferences and tissue distributions. Both are generally cytosolic and are thought to associate with ribosomes to modify nascent polypeptides as they emerge.

Substrates include many signaling and regulatory proteins, and N-myristoylation is important for proper localization and function. Loss or inhibition of NMT activity can disrupt signaling, development, and cell viability in model organisms, and may contribute to disease processes when dysregulated.

Therapeutic relevance: NMT inhibitors have been investigated as potential anti-cancer, anti-viral, and anti-parasitic agents. Several small molecules can block NMT activity in vitro and in cells, sometimes with selectivity for one isozyme. Research continues to assess safety, efficacy, and resistance mechanisms.

Evolution and biology: NMT1 is conserved across eukaryotes, illustrating the widespread importance of myristoylation. In many species, NMT activity is essential for viability, reflecting its central role in membrane targeting and signaling.