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 journalArticle

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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.

LanguageEnglish
Pages292-302
Number of pages11
JournalFEBS Open Bio
Volume5
Issue number1
DOIs
StatusPublished - Jan 2015

Fingerprint

Caenorhabditis elegans
Proline
Catalytic Domain
Crystal structure
Peptides
Enzymes
Exopeptidases
Imino Acids
Aminopeptidases
Dimers
Zinc
Peptide Hydrolases
Tissue
Amino Acids
Substrates
X-Pro aminopeptidase

Keywords

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

Cite this

Iyer, S., La-Borde, P. J., Payne, K. A. P., Parsons, M. R., Turner, A. J., Isaac, R. E., & Acharya, K. R. (2015). Crystal structure of X-prolyl aminopeptidase from Caenorhabditis elegans: a cytosolic enzyme with a di-nuclear active site. FEBS Open Bio, 5(1), 292-302. DOI: 10.1016/j.fob.2015.03.013

Crystal structure of X-prolyl aminopeptidase from Caenorhabditis elegans : a cytosolic enzyme with a di-nuclear active site. / Iyer, Shalini; La-Borde, Penelope J.; Payne, Karl A P; Parsons, Mark R.; Turner, Anthony J.; Isaac, R. Elwyn; Acharya, K. Ravi.

In: FEBS Open Bio, Vol. 5, No. 1, 01.2015, p. 292-302.

Research output: Contribution to journalArticle

Iyer S, La-Borde PJ, Payne KAP, Parsons MR, Turner AJ, Isaac RE et al. Crystal structure of X-prolyl aminopeptidase from Caenorhabditis elegans: a cytosolic enzyme with a di-nuclear active site. FEBS Open Bio. 2015 Jan;5(1):292-302. Available from, DOI: 10.1016/j.fob.2015.03.013
Iyer, Shalini ; La-Borde, Penelope J. ; Payne, Karl A P ; Parsons, Mark R. ; Turner, Anthony J. ; Isaac, R. Elwyn ; Acharya, K. Ravi. / Crystal structure of X-prolyl aminopeptidase from Caenorhabditis elegans : a cytosolic enzyme with a di-nuclear active site. In: FEBS Open Bio. 2015 ; Vol. 5, No. 1. pp. 292-302
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