acylproteiinithioesteraasien

Acyl-protein thioesterases are enzymes that catalyze the hydrolysis of thioester bonds between fatty acyl groups, most commonly palmitoyl groups, and cysteine residues on proteins. This reaction reverses S-palmitoylation, a reversible post-translational modification that influences protein association with membranes, subcellular localization, stability, and protein–protein interactions. In cells, palmitoyltransferases of the zDHHC family attach palmitoyl groups to target proteins, while acyl-protein thioesterases remove them, enabling dynamic control of signaling pathways.

In humans, several families of acyl-protein thioesterases have been characterized. The best studied are APT1 (LYPLA1) and APT2 (LYPLA2), serine hydrolases capable of depalmitoylating a range of substrates. More recently, the ABHD17A, ABHD17B, and ABHD17C enzymes have been identified as additional depalmitoylases with distinct substrate preferences, including neuronal and synaptic proteins such as PSD-95 and certain G-protein subunits. These enzymes differ in cellular localization, substrate range, and regulatory context, contributing to tissue- and pathway-specific palmitoylation dynamics.

Biological significance of acyl-protein thioesterases lies in their ability to regulate the localization and activity of signaling proteins through reversible depalmitoylation. This dynamic cycle affects G protein–coupled receptor signaling, Ras-family signaling, and synaptic organization, among other processes. Dysregulation of depalmitoylation has been associated with various diseases, including cancer and neurological disorders.

Research tools include small-molecule inhibitors (for example, inhibitors used to block depalmitoylation in cells) and activity-based profiling to identify substrates and measure enzyme activity, supporting ongoing exploration of their roles and therapeutic potential.