X-prolyl aminopeptidase 1 (XPNPEP1)

X-prolyl aminopeptidase 1 (XPNPEP1) is a cytosolic metalloaminopeptidase that catalyzes the cleavage of N-terminal amino acids from peptides where the second residue is proline, a bond that most peptidases cannot hydrolyze[1][3][5]. It is essential for the maturation and breakdown of various bioactive peptides, including peptide hormones, neuropeptides, tachykinins, and fragments of dietary proteins[3][5]. The enzyme operates as a manganese-dependent homodimer in humans, features a unique three-domain structure, and has been implicated in cardiovascular pathophysiology through its role in bradykinin inactivation, as well as in some renal and metabolic disorders when deficient[1][5]. Experimental inhibitors like apstatin bind to the metal center and block substrate processing, providing a tool for mechanistic study[2]. The gene encoding XPNPEP1 is located on chromosome 10q25.1 and produces multiple splicing variants[5]. Proteome and structural analyses show that the enzyme shares conserved mechanisms and substrate specificity with other X-prolyl peptidases[1][2].

Other names

Xaa-Pro aminopeptidase 1Aminoacylproline aminopeptidaseSoluble aminopeptidase PAPP1SAMPXPNPEPXPNPEPLXPNPEPL1Cytosolic aminopeptidase PX-prolyl aminopeptidase (aminopeptidase P) 1, soluble

Inhibition of X-prolyl aminopeptidase 1 blocks the removal of N-terminal amino acids from peptides that have a penultimate proline, which can impact the catabolism of biologically active peptides such as bradykinin[1][2][5].