Prolyl oligopeptidase family (POP family)

The prolyl peptidase family, primarily represented by the S9 family of serine proteases, comprises enzymes characterized by their ability to hydrolyze peptide bonds involving proline residues (UniProt, 2023). Proline's unique imino acid structure makes these bonds resistant to most general proteases, allowing prolyl peptidases to act as specialized regulators of bioactive peptides (PubMed, PMID: 15554167). Prominent members include dipeptidyl peptidase 4 (DPP4), fibroblast activation protein (FAP), and prolyl endopeptidase (PREP) (NIH, 2024). These enzymes play pivotal roles in diverse biological processes such as glucose homeostasis, extracellular matrix remodeling, and neuropeptide signaling. Clinically, the family is most notable for the success of DPP4 inhibitors in treating type 2 diabetes by stabilizing incretin hormones like GLP-1 (StatPearls, 2023). Additionally, FAP is targeted in oncology due to its high expression in tumor-associated fibroblasts, while PREP is a target of interest for neurodegenerative disorders like Parkinson's disease due to its role in protein aggregation and cognitive function (PubMed, PMID: 31203189).

Other names

Prolyl endopeptidase familyS9 family of serine proteasesPost-proline cleaving enzymesProlyl peptidase family

Inhibition of enzyme activity to prevent the degradation of bioactive peptides (such as GLP-1) or to modulate the processing of signaling molecules involved in cell growth, inflammation, and protein aggregation.