Acyl-protein thioesterase
Crystal structure of human APT1, PDB code 1fj2. Alpha helices are in red, beta strands in gold, catalytic site residues in black. The 2 different monomers of the dimer are shaded in green and brown.
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| Identifiers | |||||||||
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| Symbol | Acyl-protein thioesterases (APTs) | ||||||||
| Pfam | PF02230 | ||||||||
| InterPro | IPR029058 | ||||||||
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| Available protein structures: | |
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| Pfam | structures |
| PDB | RCSB PDB; PDBe; PDBj |
| PDBsum | structure summary |
Acyl-protein thioesterases are enzymes that cleave off lipid modifications on proteins, located on the sulfur atom of cysteine residues linked via a thioester bond. Acyl-protein thioesterases are part of the α/β hydrolase superfamily of proteins and have a conserved catalytic triad. For that reason, acyl-protein thioesterases are also able to hydrolyze oxygen-linked ester bonds.
Acyl-protein thioesterases are involved in the depalmitoylation of proteins, meaning they cleave off palmitoyl modifications on proteins' cysteine residues. Cellular targets include trimeric G-alpha proteins,ion channels and GAP-43. Moreover, human acyl-protein thioesterases 1 and 2 have been identified as major components in controlling the palmitoylation cycle of the oncogene Ras. Depalmitoylation of Ras by acyl-protein thioesterases potentially reduces Ras' affinity to endomembranes, allowing it to be palmitoylated again at the Golgi apparatus and to be directed to the plasma membrane. Acyl-protein thioesterases, therefore, are thought to correct potential mislocalization of Ras.
Acyl-protein thioesterases feature 3 major structural components that determine protein function and substrate processing: 1. A conserved, classical catalytic triad to break ester and thioester bonds; 2. A long hydrophobic substrate tunnel to accommodate the palmitoyl moiety, as identified in the crystal structures of human acyl-protein thioesterase 1, human acyl-protein thioesterase 2 and Zea mays acyl-protein thioesterase 2; 3. A lid-loop that covers the catalytic site, is highly flexible and is a main factor determining the enzyme's product release rate.
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