peptidyl-lysine N6-myristoyltransferase activity

Definition

Target type: molecularfunction

Catalysis of the transfer of a myristoyl group to the N6 nitrogen atom on a lysine residue of a peptide or protein molecule. [GOC:mah, PMID:1402651]

Peptidyl-lysine N6-myristoyltransferase activity is a crucial enzymatic process involved in the covalent attachment of myristate, a 14-carbon saturated fatty acid, to the N-terminal glycine residue of a protein. This modification, known as myristoylation, is essential for the proper localization and function of many cellular proteins. The enzyme responsible for this reaction is myristoyl-CoA:protein N-myristoyltransferase (NMT).

Myristoylation typically occurs on proteins that lack an N-terminal signal sequence for entry into the endoplasmic reticulum (ER) and are destined for the plasma membrane or other cellular compartments. The myristate moiety acts as a hydrophobic anchor, facilitating the interaction of the protein with the lipid bilayer of the membrane. This anchoring mechanism is critical for the proper targeting and membrane association of numerous proteins involved in diverse cellular processes.

The process of myristoylation begins with the activation of myristate by its conjugation to coenzyme A (CoA), forming myristoyl-CoA. The NMT enzyme then catalyzes the transfer of the myristate moiety from myristoyl-CoA to the N-terminal glycine residue of the target protein. The reaction involves the formation of an amide bond between the carboxyl group of myristate and the amino group of the glycine residue.

The NMT enzyme exhibits a high degree of specificity for glycine as the target amino acid. This specificity arises from the presence of a hydrophobic pocket within the active site of the enzyme that specifically binds to the glycine residue. The presence of a glycine residue at the N-terminus of the protein is therefore a critical determinant for myristoylation.

Myristoylation plays a vital role in a wide range of cellular processes, including signal transduction, protein-protein interactions, membrane trafficking, and cytoskeletal organization. Many proteins involved in these processes, such as Src kinases, G proteins, and Ras GTPases, require myristoylation for their proper function. Dysregulation of myristoylation has been implicated in various diseases, including cancer and neurodegenerative disorders.

In summary, peptidyl-lysine N6-myristoyltransferase activity is a crucial enzymatic process that adds a myristate group to the N-terminal glycine residue of specific proteins. This modification plays a vital role in protein localization, membrane association, and function, thereby contributing to a wide range of cellular processes. Dysregulation of myristoylation can have significant implications for human health.'
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Proteins (2)

Compounds (3)