Palmitoyl-protein_thioesterase

Family: Palmitoyl-protein_thioesterase

Block: X

Parent Family: No family

Comment

Palmitoyl protein thioesterases are enzymes (EC 3.1.2.22) that remove thioester-linked fatty acyl groups such as palmitate from modified cysteine residues in proteins or peptides during lysosomal degradation. PPT1 is responsible for the removal of a palmitate group from its substrate proteins, which may include presynaptic proteins like SNAP-25, cysteine string protein (CSP), dynamin, and synaptotagmin. PPT2 removes thioester-linked fatty acyl groups from various substrates including S-palmitoyl-CoA. PPT1 and -2 perform non-redundant roles in lysosomal thioester catabolism. Neuronal ceroid lipofuscinoses (NCL) represent a group of encephalopathies that occur in 1 in 12,500 children. Mutations in the palmitoyl protein thioesterase gene (human-PPT1) causing infantile neuronal ceroid lipofuscinosis. The most common mutation results in intracellular accumulation of the polypeptide and undetectable enzyme activity in the brain. Insensitive to commonly used serine-modifying reagents phenylmethylsulfonyl fluoride (PMSF) and diisopropylfluorophosphate. See paper of structure of bovine enzyme 1EXW (Das et al. 2000). PPT2 deficiency in a recent transgenic mouse model is associated with a form of neuronal ceroid lipofuscinosis, suggesting that PPT1 and -2 perform non-redundant roles in lysosomal thioester catabolism. Peptide based reversible inhibitors may have a role as chaperone that could facilitate the transport of mutant PPT1 variants to the lysosome where improved enzyme stability may be observed in the lower pH environment Family TE20 in ThYme database