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 active Caenorhabditis 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 that C. elegans APP-1 shares similar mode of substrate binding and a common catalytic mechanism with other known X-prolyl aminopeptidases.
Original language | English |
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Pages (from-to) | 292–302 |
Journal | FEBS Open Bio |
Volume | 5 |
Issue number | 1 |
Early online date | 2 Apr 2015 |
DOIs | |
Publication status | E-pub ahead of print - 2 Apr 2015 |
Keywords
- APP1
- aminopeptidase P1
- CCP4
- computational collaborative project 4
- ICP-AES
- inductively coupled plasma atomic emission spectroscopy
- ICP-MS
- MAP
- inductively coupled plasma mass spectrometry
- methionine aminopeptidase
- NMR
- nuclear magnetic resonance
- PCR
- polymerase chain reaction
- PEG3350
- polyethylene glycol 3350
- rmsd
- root mean square deviation
- XPNPEP
- X-prolyl aminopeptidase
- Apstatin
- Di-nuclear active site
- Protease inhibitor
- X-ray crystallography
- Zinc metalloprotease