X-Prolyl Aminopeptidase 3 (XPNPEP3)

XPNPEP3 belongs to a family of X-pro-aminopeptidases that utilize a metal cofactor and remove the N-terminal amino acid from peptides with a proline residue in the penultimate position. The deduced 507-amino acid protein has a calculated molecular mass of 57 kD. APP3 had an N-terminal mitochondrial targeting sequence with 2 sites for proteolytic cleavage, and a C-terminal catalytic domain. Overall, APP3 shares 33% sequence identity with E. coli App, but only 12% and 16% identity, respectively, with human APP1 (XPNPEP1) or APP2 (XPNPEP2). Both E. coli App and human APP3 have 2 Mn(2+)-binding sites, 3 residues that contribute to proline binding, 2 histidines required for catalysis, and a dead-end residue for substrate binding that ensures cleavage of an X-pro bond only if X is the N-terminal amino acid.