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Homology modeling and virtual screening approaches to identify potent inhibitors of VEB-1 β-lactamase
BACKGROUND: bla(VEB-1) is an integron-located extended-spectrum β-lactamase gene initially detected in Escherichia coli and Pseudomonas aeruginosa strains from south-east Asia. Several recent studies have reported that VEB-1-positive strains are highly resistant to ceftazidime, cefotaxime and aztreo...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668210/ https://www.ncbi.nlm.nih.gov/pubmed/23547944 http://dx.doi.org/10.1186/1742-4682-10-22 |
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author | Messaoudi, Abdelmonaem Belguith, Hatem Ben Hamida, Jeannette |
author_facet | Messaoudi, Abdelmonaem Belguith, Hatem Ben Hamida, Jeannette |
author_sort | Messaoudi, Abdelmonaem |
collection | PubMed |
description | BACKGROUND: bla(VEB-1) is an integron-located extended-spectrum β-lactamase gene initially detected in Escherichia coli and Pseudomonas aeruginosa strains from south-east Asia. Several recent studies have reported that VEB-1-positive strains are highly resistant to ceftazidime, cefotaxime and aztreonam antibiotics. One strategy to overcome resistance involves administering antibiotics together with β-lactamase inhibitors during the treatment of infectious diseases. During this study, four VEB-1 β-lactamase inhibitors were identified using computer-aided drug design. METHODS: The SWISS-MODEL tool was utilized to generate three dimensional structures of VEB-1 β-lactamase, and the 3D model VEB-1 was verified using PROCHECK, ERRAT and VERIFY 3D programs. Virtual screening was performed by docking inhibitors obtained from the ZINC Database to the active site of the VEB-1 protein using AutoDock Vina software. RESULTS AND CONCLUSION: Homology modeling studies were performed to obtain a three-dimensional structure of VEB-1 β-lactamase. The generated model was validated, and virtual screening of a large chemical ligand library with docking simulations was performed using AutoDock software with the ZINC database. On the basis of the dock-score, four molecules were subjected to ADME/TOX analysis, with ZINC4085364 emerging as the most potent inhibitor of the VEB-1 β-lactamase. |
format | Online Article Text |
id | pubmed-3668210 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-36682102013-06-03 Homology modeling and virtual screening approaches to identify potent inhibitors of VEB-1 β-lactamase Messaoudi, Abdelmonaem Belguith, Hatem Ben Hamida, Jeannette Theor Biol Med Model Research BACKGROUND: bla(VEB-1) is an integron-located extended-spectrum β-lactamase gene initially detected in Escherichia coli and Pseudomonas aeruginosa strains from south-east Asia. Several recent studies have reported that VEB-1-positive strains are highly resistant to ceftazidime, cefotaxime and aztreonam antibiotics. One strategy to overcome resistance involves administering antibiotics together with β-lactamase inhibitors during the treatment of infectious diseases. During this study, four VEB-1 β-lactamase inhibitors were identified using computer-aided drug design. METHODS: The SWISS-MODEL tool was utilized to generate three dimensional structures of VEB-1 β-lactamase, and the 3D model VEB-1 was verified using PROCHECK, ERRAT and VERIFY 3D programs. Virtual screening was performed by docking inhibitors obtained from the ZINC Database to the active site of the VEB-1 protein using AutoDock Vina software. RESULTS AND CONCLUSION: Homology modeling studies were performed to obtain a three-dimensional structure of VEB-1 β-lactamase. The generated model was validated, and virtual screening of a large chemical ligand library with docking simulations was performed using AutoDock software with the ZINC database. On the basis of the dock-score, four molecules were subjected to ADME/TOX analysis, with ZINC4085364 emerging as the most potent inhibitor of the VEB-1 β-lactamase. BioMed Central 2013-04-02 /pmc/articles/PMC3668210/ /pubmed/23547944 http://dx.doi.org/10.1186/1742-4682-10-22 Text en Copyright © 2013 Messaoudi et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Messaoudi, Abdelmonaem Belguith, Hatem Ben Hamida, Jeannette Homology modeling and virtual screening approaches to identify potent inhibitors of VEB-1 β-lactamase |
title | Homology modeling and virtual screening approaches to identify potent inhibitors of VEB-1 β-lactamase |
title_full | Homology modeling and virtual screening approaches to identify potent inhibitors of VEB-1 β-lactamase |
title_fullStr | Homology modeling and virtual screening approaches to identify potent inhibitors of VEB-1 β-lactamase |
title_full_unstemmed | Homology modeling and virtual screening approaches to identify potent inhibitors of VEB-1 β-lactamase |
title_short | Homology modeling and virtual screening approaches to identify potent inhibitors of VEB-1 β-lactamase |
title_sort | homology modeling and virtual screening approaches to identify potent inhibitors of veb-1 β-lactamase |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668210/ https://www.ncbi.nlm.nih.gov/pubmed/23547944 http://dx.doi.org/10.1186/1742-4682-10-22 |
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