Pyroglutamyl peptidase (PGP) type I, also known as Pyrrolidone-Carboxylate Peptidase (PCP), is an enzyme that selectively removes pyrrolidone carboxylic acid (PCA), also called pyroglutamate (pGlu), from N-terminus of peptides and proteins. N-terminal glutamine residue can spontaneously become pyroglutamate (pGlu), and protect these proteins from proteolysis by other proteases until a PCP removes the pGlu. The PCP is common in many bacteria, and less usual for plant, animal and human tissues. The enzyme belongs to the cysteine peptidase family, with the common Cys-His-Asp catalytic triad. There are several structures of homologous proteins deposited in the PDB, which are homo tetramers and it was postulated that the functional unit is a tetramer. In this crystal structure of PCP from Staphylococcus aureus, the protein forms dimer. It is not clear whether the functional form is a monomer, dimer, or tetramer.
The product of hydrolysis, a Pyroglutamic Acid, improves blood circulation in the brain, and is sold as “smart drug”. Derivatives of PCA, Pyrrolidones, are used for neuroprotection after stroke and as antiepileptic agents.