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Crystal structure of the human carbonic anhydrase II adduct with 1-(4-sulfamoylphenyl-ethyl)-2,4,6-triphenylpyridinium perchlorate, a membrane-impermeant, isoform selective inhibitor
Pyridinium containing sulfonamides have been largely investigated as carbonic anhydrase inhibitors (CAIs), showing interesting selectivity features. Nevertheless, only few structural studies are so far available on adducts that these compounds form with diverse CA isoforms. In this paper, we report...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011996/ https://www.ncbi.nlm.nih.gov/pubmed/29199489 http://dx.doi.org/10.1080/14756366.2017.1405263 |
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author | Alterio, Vincenzo Esposito, Davide Monti, Simona Maria Supuran, Claudiu T. De Simone, Giuseppina |
author_facet | Alterio, Vincenzo Esposito, Davide Monti, Simona Maria Supuran, Claudiu T. De Simone, Giuseppina |
author_sort | Alterio, Vincenzo |
collection | PubMed |
description | Pyridinium containing sulfonamides have been largely investigated as carbonic anhydrase inhibitors (CAIs), showing interesting selectivity features. Nevertheless, only few structural studies are so far available on adducts that these compounds form with diverse CA isoforms. In this paper, we report the structural characterization of the adduct that a triphenylpyridinium derivative forms with hCA II, showing that the substitution of the pyridinium ring plays a key role in determining the conformation of the inhibitor in the active site and consequently the binding affinity to the enzyme. These findings open new perspectives on the basic structural requirements for designing sulfonamide CAIs with a selective inhibition profile. |
format | Online Article Text |
id | pubmed-7011996 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-70119962020-02-24 Crystal structure of the human carbonic anhydrase II adduct with 1-(4-sulfamoylphenyl-ethyl)-2,4,6-triphenylpyridinium perchlorate, a membrane-impermeant, isoform selective inhibitor Alterio, Vincenzo Esposito, Davide Monti, Simona Maria Supuran, Claudiu T. De Simone, Giuseppina J Enzyme Inhib Med Chem Short Communication Pyridinium containing sulfonamides have been largely investigated as carbonic anhydrase inhibitors (CAIs), showing interesting selectivity features. Nevertheless, only few structural studies are so far available on adducts that these compounds form with diverse CA isoforms. In this paper, we report the structural characterization of the adduct that a triphenylpyridinium derivative forms with hCA II, showing that the substitution of the pyridinium ring plays a key role in determining the conformation of the inhibitor in the active site and consequently the binding affinity to the enzyme. These findings open new perspectives on the basic structural requirements for designing sulfonamide CAIs with a selective inhibition profile. Taylor & Francis 2017-12-04 /pmc/articles/PMC7011996/ /pubmed/29199489 http://dx.doi.org/10.1080/14756366.2017.1405263 Text en © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Short Communication Alterio, Vincenzo Esposito, Davide Monti, Simona Maria Supuran, Claudiu T. De Simone, Giuseppina Crystal structure of the human carbonic anhydrase II adduct with 1-(4-sulfamoylphenyl-ethyl)-2,4,6-triphenylpyridinium perchlorate, a membrane-impermeant, isoform selective inhibitor |
title | Crystal structure of the human carbonic anhydrase II adduct with 1-(4-sulfamoylphenyl-ethyl)-2,4,6-triphenylpyridinium perchlorate, a membrane-impermeant, isoform selective inhibitor |
title_full | Crystal structure of the human carbonic anhydrase II adduct with 1-(4-sulfamoylphenyl-ethyl)-2,4,6-triphenylpyridinium perchlorate, a membrane-impermeant, isoform selective inhibitor |
title_fullStr | Crystal structure of the human carbonic anhydrase II adduct with 1-(4-sulfamoylphenyl-ethyl)-2,4,6-triphenylpyridinium perchlorate, a membrane-impermeant, isoform selective inhibitor |
title_full_unstemmed | Crystal structure of the human carbonic anhydrase II adduct with 1-(4-sulfamoylphenyl-ethyl)-2,4,6-triphenylpyridinium perchlorate, a membrane-impermeant, isoform selective inhibitor |
title_short | Crystal structure of the human carbonic anhydrase II adduct with 1-(4-sulfamoylphenyl-ethyl)-2,4,6-triphenylpyridinium perchlorate, a membrane-impermeant, isoform selective inhibitor |
title_sort | crystal structure of the human carbonic anhydrase ii adduct with 1-(4-sulfamoylphenyl-ethyl)-2,4,6-triphenylpyridinium perchlorate, a membrane-impermeant, isoform selective inhibitor |
topic | Short Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011996/ https://www.ncbi.nlm.nih.gov/pubmed/29199489 http://dx.doi.org/10.1080/14756366.2017.1405263 |
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