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Xenon for tunnelling analysis of the efflux pump component OprN
Tripartite efflux pumps are among the main actors responsible for antibiotics resistance in Gram-negative bacteria. In the last two decades, structural studies gave crucial information about the assembly interfaces and the mechanistic motions. Thus rigidifying the assembly seems to be an interesting...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5590881/ https://www.ncbi.nlm.nih.gov/pubmed/28886086 http://dx.doi.org/10.1371/journal.pone.0184045 |
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author | Ntsogo Enguéné, Yvette Véronique Phan, Gilles Garnier, Cyril Ducruix, Arnaud Prangé, Thierry Broutin, Isabelle |
author_facet | Ntsogo Enguéné, Yvette Véronique Phan, Gilles Garnier, Cyril Ducruix, Arnaud Prangé, Thierry Broutin, Isabelle |
author_sort | Ntsogo Enguéné, Yvette Véronique |
collection | PubMed |
description | Tripartite efflux pumps are among the main actors responsible for antibiotics resistance in Gram-negative bacteria. In the last two decades, structural studies gave crucial information about the assembly interfaces and the mechanistic motions. Thus rigidifying the assembly seems to be an interesting way to hamper the drug efflux. In this context, xenon is a suitable probe for checking whether small ligands could act as conformational lockers by targeting hydrophobic cavities. Here we focus on OprN, the outer membrane channel of the MexEF efflux pump from Pseudomonas aeruginosa. After exposing OprN crystals to xenon gas pressure, 14 binding sites were observed using X-ray crystallography. These binding sites were unambiguously characterized in hydrophobic cavities of OprN. The major site is observed in the sensitive iris-like region gating the channel at the periplasmic side, built by the three key-residues Leu 405, Asp 109, and Arg 412. This arrangement defines along the tunnel axis a strong hydrophobic/polar gradient able to enhance the passive efflux mechanism of OprN. The other xenon atoms reveal strategic hydrophobic regions of the channel scaffold to target, with the aim to freeze the dynamic movements responsible of the open/close conformational equilibrium in OprN. |
format | Online Article Text |
id | pubmed-5590881 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-55908812017-09-15 Xenon for tunnelling analysis of the efflux pump component OprN Ntsogo Enguéné, Yvette Véronique Phan, Gilles Garnier, Cyril Ducruix, Arnaud Prangé, Thierry Broutin, Isabelle PLoS One Research Article Tripartite efflux pumps are among the main actors responsible for antibiotics resistance in Gram-negative bacteria. In the last two decades, structural studies gave crucial information about the assembly interfaces and the mechanistic motions. Thus rigidifying the assembly seems to be an interesting way to hamper the drug efflux. In this context, xenon is a suitable probe for checking whether small ligands could act as conformational lockers by targeting hydrophobic cavities. Here we focus on OprN, the outer membrane channel of the MexEF efflux pump from Pseudomonas aeruginosa. After exposing OprN crystals to xenon gas pressure, 14 binding sites were observed using X-ray crystallography. These binding sites were unambiguously characterized in hydrophobic cavities of OprN. The major site is observed in the sensitive iris-like region gating the channel at the periplasmic side, built by the three key-residues Leu 405, Asp 109, and Arg 412. This arrangement defines along the tunnel axis a strong hydrophobic/polar gradient able to enhance the passive efflux mechanism of OprN. The other xenon atoms reveal strategic hydrophobic regions of the channel scaffold to target, with the aim to freeze the dynamic movements responsible of the open/close conformational equilibrium in OprN. Public Library of Science 2017-09-08 /pmc/articles/PMC5590881/ /pubmed/28886086 http://dx.doi.org/10.1371/journal.pone.0184045 Text en © 2017 Ntsogo Enguéné et al 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 author and source are credited. |
spellingShingle | Research Article Ntsogo Enguéné, Yvette Véronique Phan, Gilles Garnier, Cyril Ducruix, Arnaud Prangé, Thierry Broutin, Isabelle Xenon for tunnelling analysis of the efflux pump component OprN |
title | Xenon for tunnelling analysis of the efflux pump component OprN |
title_full | Xenon for tunnelling analysis of the efflux pump component OprN |
title_fullStr | Xenon for tunnelling analysis of the efflux pump component OprN |
title_full_unstemmed | Xenon for tunnelling analysis of the efflux pump component OprN |
title_short | Xenon for tunnelling analysis of the efflux pump component OprN |
title_sort | xenon for tunnelling analysis of the efflux pump component oprn |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5590881/ https://www.ncbi.nlm.nih.gov/pubmed/28886086 http://dx.doi.org/10.1371/journal.pone.0184045 |
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