NAD-dependent protein depalmitoylase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: N6-octadecanoyl-L-lysyl-[protein] + NAD+ + H2O = octadecanoyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide. [PMID:23552949, RHEA:70563]

NAD-dependent protein depalmitoylase activity is a critical enzymatic function involved in the removal of palmitic acid, a saturated fatty acid, from proteins. This process, known as depalmitoylation, plays a vital role in regulating protein function, localization, and interactions.

Palmitoylation is a reversible post-translational modification where palmitic acid is attached to cysteine residues in proteins. This modification can alter protein conformation, enhance membrane association, and facilitate protein-protein interactions.

NAD-dependent protein depalmitoylases, also known as acyl-protein thioesterases, utilize NAD+ as a cofactor to catalyze the hydrolysis of the thioester bond between palmitic acid and cysteine residues. The enzyme's active site contains a catalytic triad of amino acids, typically consisting of a serine, a histidine, and an aspartate residue, that facilitate the hydrolysis reaction.

The removal of palmitic acid by NAD-dependent protein depalmitoylases can have profound effects on protein function. Depalmitoylation can disrupt membrane association, alter protein-protein interactions, and expose cryptic signaling motifs, leading to changes in protein activity, localization, and stability.

This enzymatic activity is crucial in a wide range of cellular processes, including:

* **Signal transduction:** Depalmitoylation regulates the activity of signaling proteins, such as G protein-coupled receptors and Ras GTPases, by modulating their membrane association and interactions with downstream effectors.
* **Protein trafficking:** Depalmitoylation controls the localization and transport of proteins by influencing their interactions with chaperones and trafficking machinery.
* **Cellular morphology:** Depalmitoylation influences the organization and dynamics of cellular structures, such as the cytoskeleton and lipid rafts.

Defects in NAD-dependent protein depalmitoylase activity can lead to a range of cellular dysfunction and contribute to the development of various diseases, including cancer, neurodegenerative disorders, and metabolic diseases.

In summary, NAD-dependent protein depalmitoylase activity is a crucial enzymatic process that regulates protein function, localization, and interactions by removing palmitic acid from proteins. This activity is essential for a wide range of cellular processes and plays a significant role in maintaining cellular homeostasis.'
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Proteins (2)

Compounds (42)