Crystal structure of X-prolyl aminopeptidase from Caenorhabditis elegans: A cytosolic enzyme with a di-nuclear active site.

Shalini Iyer, Penelope J La-Borde, Karl A P Payne, Mark R Parsons, Anthony J Turner, R Elwyn Isaac, K Ravi Acharya

    Research output: Contribution to journalArticlepeer-review

    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 languageEnglish
    JournalFEBS open bio
    Volume5
    DOIs
    Publication statusPublished - 2015

    Keywords

    • APP1, aminopeptidase P1
    • Apstatin
    • CCP4, computational collaborative project 4
    • Di-nuclear active site
    • ICP-AES, inductively coupled plasma atomic emission spectroscopy
    • ICP-MS, inductively coupled plasma mass spectrometry
    • MAP, methionine aminopeptidase
    • NMR, nuclear magnetic resonance
    • PCR, polymerase chain reaction
    • PEG3350, polyethylene glycol 3350
    • Protease inhibitor
    • X-prolyl aminopeptidase
    • X-ray crystallography
    • XPNPEP, X-prolyl aminopeptidase
    • Zinc metalloprotease
    • rmsd, root mean square deviation

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