Nmyristoyltransferaasi

Nmyristoyltransferase (NMT), also known as N-myristoyltransferase or N-myristoyl-CoA:protein N-myristoyltransferase, is an enzyme that catalyzes the transfer of a myristoyl group from myristoyl-CoA to the N-terminal glycine residue of certain proteins. This post-translational modification, called myristoylation, is essential for the proper localization, function, and stability of numerous proteins in eukaryotic cells.

NMT is a key enzyme in the myristoylation pathway, which begins with the activation of myristic acid (a 14-carbon saturated fatty acid) to myristoyl-CoA. The enzyme then transfers the myristoyl group to the N-terminal glycine of target proteins, typically those involved in signal transduction, membrane trafficking, and cytoskeletal dynamics. Myristoylation is often irreversible and plays a critical role in protein targeting to membranes, particularly in the case of proteins that lack intrinsic hydrophobic domains.

In humans, there are two isoforms of NMT: NMT1 and NMT2, encoded by the *NMT1* and *NMT2* genes, respectively. These isoforms exhibit distinct tissue expression patterns and substrate specificities, though they share high sequence similarity. NMT1 is widely expressed, while NMT2 is predominantly found in the brain and testis. Both isoforms are essential for embryonic development, as demonstrated by knockout studies in model organisms.

NMT inhibitors have been explored as potential therapeutic agents, particularly for targeting oncogenic proteins that rely on myristoylation for their function. These inhibitors disrupt protein myristoylation, leading to mislocalization and degradation of target proteins. However, the broad specificity of NMT raises challenges in developing selective inhibitors without off-target effects.

Structurally, NMT belongs to the superfamily of GNAT (G-protein-coupled receptor regulator-like) enzymes, characterized by a conserved fold that facilitates substrate binding and catalysis. The enzyme’s active site accommodates both myristoyl-CoA and the N-terminal glycine of the substrate, ensuring precise transfer of the myristoyl group. Dysregulation of NMT activity has been implicated in various diseases, including cancer and neurodegenerative disorders, highlighting its importance in cellular physiology.