Pyroglutamyl-peptidase I (PGPEP1)

Pyroglutamyl-peptidase I (PGPEP1) is a cytosolic cysteine protease belonging to the peptidase C15 family, found in humans and widely across species. This enzyme selectively cleaves N-terminal pyroglutamate (pGlu) residues from bioactive peptides and proteins, including several hypothalamic hormones such as thyrotropin-releasing hormone (TRH) and luteinizing hormone-releasing hormone (LH-RH), which are otherwise resistant to degradation by conventional aminopeptidases. By regulating the removal of pGlu residues, Pyroglutamyl-peptidase I plays a role in hormone inactivation, peptide turnover, and potentially nutrient assimilation, primarily in lower organisms. The enzyme is characterized by a catalytic triad (Cys-His-Asp/Glu) and does not conform to the typical oxyanion hole seen in many cysteine proteases. Its expression and activity are altered in various disease conditions, and it is being studied for roles in cancer biology and male infertility as well as a general marker of peptide metabolism.

Other names

Pyroglutamyl-peptidase 1PGPIPAP-IPGP-IPcpPGP5-oxoprolyl-peptidasePyroglutamyl aminopeptidase IPyrrolidone-carboxylate peptidasePYRase2810003H13RIKGm19458LOC100502927MGC10812

Proteolytic removal of N-terminal pyroglutamyl residue via catalytic triad (Cys-His-Asp/Glu)