Aminopeptidase P

Aminopeptidase P (AP-P; X-Pro aminopeptidase) has the unique ability to leave the N-terminal amino acid residue from peptides having proline as the penultimate amino acid residue. Biologically active peptides comprise an important and diverse class of extracellular chemical messengers that mediate a wide range of intercellular interactions. Several bioactive peptides including hormones, neuropeptides, neurotransmitters escape non-specific protease degradation by having an Xaa-Pro motif at their amino termini. Due to its cyclic nature, proline confers resistance to such peptide bonds so that aminopeptidases with broad specificity cannot act upon such peptides. There are a limited number of peptidases that act on peptide bonds involving a proline residue, such as dipeptidyl peptidase II (DPPII) and dipeptidyl peptidase W (DPPIV), and prolidase (which cleaves the Xaa-Pro bond only in dipeptides), or endopeptidases such as prolyl endopeptidase (which cleaves on the carbonyl side of proline residues within a protein or peptide). However,of these enzymes have been reported to hydrolyze Xaa-Pro bonds located at the N-terminus of peptides and proteins. Therefore, role of AP-P is crucial in this respect. AP-P activity is ubiquitous and has been found in a wide range of organisms including bacteria, yeast and vertebrates. Mammalian AP-Ps exist in membrane-bound and cytosolic forms, which represent two distinct gene products. The cytosolic (soluble) form of aminopeptidase P is found in human leukocytes and rat brain.