ZDHHC Inhibitors

Zinc finger DHHC-type palmitoyltransferases (ZDHHCs) are a family of enzymes that play a critical role in the post-translational modification of proteins through palmitoylation. This enzymatic process involves the addition of palmitic acid, a saturated fatty acid, to specific cysteine residues on target proteins. Palmitoylation by ZDHHCs is crucial for regulating the localization, stability, and function of a wide range of proteins, including those involved in signaling pathways, membrane trafficking, and cell communication. The activity of ZDHHCs is characterized by the presence of a conserved DHHC cysteine-rich domain, which is essential for their catalytic function. Through their action, ZDHHCs modulate various cellular processes, contributing to the dynamic nature of cellular membranes and protein interactions within the cell.

Targeting Zinc finger DHHC-type palmitoyltransferases (ZDHHCs) for disruption or inhibition is a strategy aimed at modulating the palmitoylation status of proteins, thereby impacting their function and cellular behavior. Small molecule inhibitors such as 2-Bromopalmitate and Palmostatin B are used to inhibit the enzymatic activity of ZDHHCs, either by blocking the active site or by interfering with substrate binding. These inhibitors can lead to altered protein localization and function, as palmitoylation often dictates membrane association of proteins. The disruption of ZDHHC activity has implications for studying the role of protein palmitoylation in various cellular processes, including signal transduction, membrane dynamics, and intracellular trafficking.