Crystal structure of X‐prolyl aminopeptidase fromCaenorhabditis elegans: A cytosolic enzyme with a di‐nuclear active site
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 cata...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | FEBS Open Bio |
| Subjects: | |
| Online Access: | https://doi.org/10.1016/j.fob.2015.03.013 |
| _version_ | 1811185103893692416 |
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| author | Shalini Iyer Penelope J. La-Borde Karl A.P. Payne Mark R. Parsons Anthony J. Turner R. Elwyn Isaac K. Ravi Acharya |
| author_facet | Shalini Iyer Penelope J. La-Borde Karl A.P. Payne Mark R. Parsons Anthony J. Turner R. Elwyn Isaac K. Ravi Acharya |
| author_sort | Shalini Iyer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T13:23:43Z |
| format | Article |
| id | doaj.art-a81b952de5dc4dc08fa330f7521a86c9 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-04-11T13:23:43Z |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-a81b952de5dc4dc08fa330f7521a86c92022-12-22T04:22:07ZengWileyFEBS Open Bio2211-54632015-01-015129230210.1016/j.fob.2015.03.013Crystal structure of X‐prolyl aminopeptidase fromCaenorhabditis elegans: A cytosolic enzyme with a di‐nuclear active siteShalini Iyer0Penelope J. La-Borde1Karl A.P. Payne2Mark R. Parsons3Anthony J. Turner4R. Elwyn Isaac5K. Ravi Acharya6Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UKDepartment of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UKFaculty of Biological Sciences, Clarendon Way, University of Leeds, Leeds LS2 9JT, UKFaculty of Biological Sciences, Clarendon Way, University of Leeds, Leeds LS2 9JT, UKFaculty of Biological Sciences, Clarendon Way, University of Leeds, Leeds LS2 9JT, UKFaculty of Biological Sciences, Clarendon Way, University of Leeds, Leeds LS2 9JT, UKDepartment of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UKEukaryotic 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.https://doi.org/10.1016/j.fob.2015.03.013ApstatinDi-nuclear active siteProtease inhibitorX-ray crystallographyX-prolyl aminopeptidaseZinc metalloprotease |
| spellingShingle | Shalini Iyer Penelope J. La-Borde Karl A.P. Payne Mark R. Parsons Anthony J. Turner R. Elwyn Isaac K. Ravi Acharya Crystal structure of X‐prolyl aminopeptidase fromCaenorhabditis elegans: A cytosolic enzyme with a di‐nuclear active site FEBS Open Bio Apstatin Di-nuclear active site Protease inhibitor X-ray crystallography X-prolyl aminopeptidase Zinc metalloprotease |
| title | Crystal structure of X‐prolyl aminopeptidase fromCaenorhabditis elegans: A cytosolic enzyme with a di‐nuclear active site |
| title_full | Crystal structure of X‐prolyl aminopeptidase fromCaenorhabditis elegans: A cytosolic enzyme with a di‐nuclear active site |
| title_fullStr | Crystal structure of X‐prolyl aminopeptidase fromCaenorhabditis elegans: A cytosolic enzyme with a di‐nuclear active site |
| title_full_unstemmed | Crystal structure of X‐prolyl aminopeptidase fromCaenorhabditis elegans: A cytosolic enzyme with a di‐nuclear active site |
| title_short | Crystal structure of X‐prolyl aminopeptidase fromCaenorhabditis elegans: A cytosolic enzyme with a di‐nuclear active site |
| title_sort | crystal structure of x prolyl aminopeptidase fromcaenorhabditis elegans a cytosolic enzyme with a di nuclear active site |
| topic | Apstatin Di-nuclear active site Protease inhibitor X-ray crystallography X-prolyl aminopeptidase Zinc metalloprotease |
| url | https://doi.org/10.1016/j.fob.2015.03.013 |
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