Crystal structure of X‐prolyl aminopeptidase fromCaenorhabditis elegans: A cytosolic enzyme with a di‐nuclear active site

Abstract

Eukaryotic aminopeptidase P1 (APP1), also known as X‐prolyl aminopeptidase (XPNPEP1) in human tissues, is a cytosolic exopeptidase that preferentially removes amino acids from the N‐terminus of peptides possessing a penultimate N‐terminal proline residue. The enzyme has an important role in the catabolism of proline containing peptides since peptide bonds adjacent to the imino acid proline are resistant to cleavage by most peptidases. We show that recombinant and catalytically activeCaenorhabditis elegans APP‐1 is a dimer that uses dinuclear zinc at the active site and, for the first time, we provide structural information for a eukaryotic APP‐1 in complex with the inhibitor, apstatin. Our analysis reveals thatC. elegans APP‐1 shares similar mode of substrate binding and a common catalytic mechanism with other known X‐prolyl aminopeptidases.

Keywords

• Apstatin
• Di-nuclear active site
• Protease inhibitor
• X-ray crystallography
• X-prolyl aminopeptidase
• Zinc metalloprotease