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Iyer S, La-Borde PJ, Payne KA, et al. Crystal structure of X-prolyl aminopeptidase from Caenorhabditis elegans: A cytosolic enzyme with a di-nuclear active site. FEBS Open Bio. 2015;5:292-302doi: 10.1016/j.fob.2015.03.013.
Iyer, S., La-Borde, P. J., Payne, K. A., 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, 5292-302. https://doi.org/10.1016/j.fob.2015.03.013
Iyer, Shalini, et al. "Crystal structure of X-prolyl aminopeptidase from Caenorhabditis elegans: A cytosolic enzyme with a di-nuclear active site." FEBS open bio vol. 5 (2015): 292-302. doi: https://doi.org/10.1016/j.fob.2015.03.013
Iyer S, La-Borde PJ, Payne KA, Parsons MR, Turner AJ, Isaac RE, Acharya KR. Crystal structure of X-prolyl aminopeptidase from Caenorhabditis elegans: A cytosolic enzyme with a di-nuclear active site. FEBS Open Bio. 2015 Apr 02;5:292-302. doi: 10.1016/j.fob.2015.03.013. eCollection 2015. PMID: 25905034; PMCID: PMC4404410.
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FEBS Open Bio. 2015 Apr 02;5:292-302. doi: 10.1016/j.fob.2015.03.013. eCollection 2015.

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

FEBS open bio

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

Affiliations

  1. Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
  2. Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK ; School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
  3. Faculty of Biological Sciences, Clarendon Way, University of Leeds, Leeds LS2 9JT, UK ; Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK.
  4. Faculty of Biological Sciences, Clarendon Way, University of Leeds, Leeds LS2 9JT, UK ; Sevenoaks School, Sevenoaks TN13 1HU, UK.
  5. Faculty of Biological Sciences, Clarendon Way, University of Leeds, Leeds LS2 9JT, UK.

PMID: 25905034 PMCID: PMC4404410 DOI: 10.1016/j.fob.2015.03.013

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.

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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