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A new high-resolution crystal structure of the Drosophila melanogaster angiotensin converting enzyme homologue, AnCE
Angiotensin converting enzyme (ACE) is a zinc-dependent dipeptidyl carboxypeptidase with an essential role in blood pressure homeostasis in mammals. ACE has long been targeted in the treatment of hypertension through ACE inhibitors, however current inhibitors are known to cause severe side effects....
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556727/ https://www.ncbi.nlm.nih.gov/pubmed/26380810 http://dx.doi.org/10.1016/j.fob.2015.08.004 |
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author | Harrison, Charlotte Acharya, K. Ravi |
author_facet | Harrison, Charlotte Acharya, K. Ravi |
author_sort | Harrison, Charlotte |
collection | PubMed |
description | Angiotensin converting enzyme (ACE) is a zinc-dependent dipeptidyl carboxypeptidase with an essential role in blood pressure homeostasis in mammals. ACE has long been targeted in the treatment of hypertension through ACE inhibitors, however current inhibitors are known to cause severe side effects. Therefore, there is a requirement for a new generation of ACE inhibitors and structural information will be invaluable in their development. ACE is a challenging enzyme to work with due to its extensive glycosylation. As such, the Drosophila melanogaster ACE homologue, AnCE, which shares ∼60% sequence similarity with human ACE, can be used as a model for studying inhibitor binding. The presence of ligands originating from the crystallisation condition at the AnCE active site has proved an obstacle to studying the binding of new inhibitor precursors. Here we present the crystal structure of AnCE (in a new crystal form) at 1.85 Å resolution, using crystals grown under different conditions. This new structure may be more suitable for studying the binding of new compounds, with the potential of developing a new generation of improved ACE inhibitors. |
format | Online Article Text |
id | pubmed-4556727 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-45567272015-09-17 A new high-resolution crystal structure of the Drosophila melanogaster angiotensin converting enzyme homologue, AnCE Harrison, Charlotte Acharya, K. Ravi FEBS Open Bio Research article Angiotensin converting enzyme (ACE) is a zinc-dependent dipeptidyl carboxypeptidase with an essential role in blood pressure homeostasis in mammals. ACE has long been targeted in the treatment of hypertension through ACE inhibitors, however current inhibitors are known to cause severe side effects. Therefore, there is a requirement for a new generation of ACE inhibitors and structural information will be invaluable in their development. ACE is a challenging enzyme to work with due to its extensive glycosylation. As such, the Drosophila melanogaster ACE homologue, AnCE, which shares ∼60% sequence similarity with human ACE, can be used as a model for studying inhibitor binding. The presence of ligands originating from the crystallisation condition at the AnCE active site has proved an obstacle to studying the binding of new inhibitor precursors. Here we present the crystal structure of AnCE (in a new crystal form) at 1.85 Å resolution, using crystals grown under different conditions. This new structure may be more suitable for studying the binding of new compounds, with the potential of developing a new generation of improved ACE inhibitors. Elsevier 2015-08-11 /pmc/articles/PMC4556727/ /pubmed/26380810 http://dx.doi.org/10.1016/j.fob.2015.08.004 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research article Harrison, Charlotte Acharya, K. Ravi A new high-resolution crystal structure of the Drosophila melanogaster angiotensin converting enzyme homologue, AnCE |
title | A new high-resolution crystal structure of the Drosophila melanogaster angiotensin converting enzyme homologue, AnCE |
title_full | A new high-resolution crystal structure of the Drosophila melanogaster angiotensin converting enzyme homologue, AnCE |
title_fullStr | A new high-resolution crystal structure of the Drosophila melanogaster angiotensin converting enzyme homologue, AnCE |
title_full_unstemmed | A new high-resolution crystal structure of the Drosophila melanogaster angiotensin converting enzyme homologue, AnCE |
title_short | A new high-resolution crystal structure of the Drosophila melanogaster angiotensin converting enzyme homologue, AnCE |
title_sort | new high-resolution crystal structure of the drosophila melanogaster angiotensin converting enzyme homologue, ance |
topic | Research article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4556727/ https://www.ncbi.nlm.nih.gov/pubmed/26380810 http://dx.doi.org/10.1016/j.fob.2015.08.004 |
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