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Systematic Mutational Analysis of the Putative Hydrolase PqsE: Toward a Deeper Molecular Understanding of Virulence Acquisition in Pseudomonas aeruginosa
Pseudomonas aeruginosa is an important opportunistic human pathogen that can establish bacterial communication by synchronizing the behavior of individual cells in a molecular phenomenon known as “quorum sensing”. Through an elusive mechanism involving gene products of the pqs operon, the PqsE enzym...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769375/ https://www.ncbi.nlm.nih.gov/pubmed/24040042 http://dx.doi.org/10.1371/journal.pone.0073727 |
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author | Folch, Benjamin Déziel, Eric Doucet, Nicolas |
author_facet | Folch, Benjamin Déziel, Eric Doucet, Nicolas |
author_sort | Folch, Benjamin |
collection | PubMed |
description | Pseudomonas aeruginosa is an important opportunistic human pathogen that can establish bacterial communication by synchronizing the behavior of individual cells in a molecular phenomenon known as “quorum sensing”. Through an elusive mechanism involving gene products of the pqs operon, the PqsE enzyme is absolutely required for the synthesis of extracellular phenazines, including the toxic blue pigment pyocyanin, effectively allowing cells to achieve full-fledged virulence. Despite several functional and structural attempts at deciphering the role of this relevant enzymatic drug target, no molecular function has yet been ascribed to PqsE. In the present study, we report a series of alanine scanning experiments aimed at altering the biological function of PqsE, allowing us to uncover key amino acid positions involved in the molecular function of this enzyme. We use sequence analysis and structural overlays with members of homologous folds to pinpoint critical positions located in the vicinity of the ligand binding cleft and surrounding environment, revealing the importance of a unique C-terminal α-helical motif in the molecular function of PqsE. Our results suggest that the active site of the enzyme involves residues that extend further into the hydrophobic core of the protein, advocating for a lid-like movement of the two terminal helices. This information should help design virtual libraries of PqsE inhibitors, providing means to counter P. aeruginosa virulence acquisition and helping to reduce nosocomial infections. |
format | Online Article Text |
id | pubmed-3769375 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-37693752013-09-13 Systematic Mutational Analysis of the Putative Hydrolase PqsE: Toward a Deeper Molecular Understanding of Virulence Acquisition in Pseudomonas aeruginosa Folch, Benjamin Déziel, Eric Doucet, Nicolas PLoS One Research Article Pseudomonas aeruginosa is an important opportunistic human pathogen that can establish bacterial communication by synchronizing the behavior of individual cells in a molecular phenomenon known as “quorum sensing”. Through an elusive mechanism involving gene products of the pqs operon, the PqsE enzyme is absolutely required for the synthesis of extracellular phenazines, including the toxic blue pigment pyocyanin, effectively allowing cells to achieve full-fledged virulence. Despite several functional and structural attempts at deciphering the role of this relevant enzymatic drug target, no molecular function has yet been ascribed to PqsE. In the present study, we report a series of alanine scanning experiments aimed at altering the biological function of PqsE, allowing us to uncover key amino acid positions involved in the molecular function of this enzyme. We use sequence analysis and structural overlays with members of homologous folds to pinpoint critical positions located in the vicinity of the ligand binding cleft and surrounding environment, revealing the importance of a unique C-terminal α-helical motif in the molecular function of PqsE. Our results suggest that the active site of the enzyme involves residues that extend further into the hydrophobic core of the protein, advocating for a lid-like movement of the two terminal helices. This information should help design virtual libraries of PqsE inhibitors, providing means to counter P. aeruginosa virulence acquisition and helping to reduce nosocomial infections. Public Library of Science 2013-09-10 /pmc/articles/PMC3769375/ /pubmed/24040042 http://dx.doi.org/10.1371/journal.pone.0073727 Text en © 2013 Folch 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Folch, Benjamin Déziel, Eric Doucet, Nicolas Systematic Mutational Analysis of the Putative Hydrolase PqsE: Toward a Deeper Molecular Understanding of Virulence Acquisition in Pseudomonas aeruginosa |
title | Systematic Mutational Analysis of the Putative Hydrolase PqsE: Toward a Deeper Molecular Understanding of Virulence Acquisition in Pseudomonas aeruginosa
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title_full | Systematic Mutational Analysis of the Putative Hydrolase PqsE: Toward a Deeper Molecular Understanding of Virulence Acquisition in Pseudomonas aeruginosa
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title_fullStr | Systematic Mutational Analysis of the Putative Hydrolase PqsE: Toward a Deeper Molecular Understanding of Virulence Acquisition in Pseudomonas aeruginosa
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title_full_unstemmed | Systematic Mutational Analysis of the Putative Hydrolase PqsE: Toward a Deeper Molecular Understanding of Virulence Acquisition in Pseudomonas aeruginosa
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title_short | Systematic Mutational Analysis of the Putative Hydrolase PqsE: Toward a Deeper Molecular Understanding of Virulence Acquisition in Pseudomonas aeruginosa
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title_sort | systematic mutational analysis of the putative hydrolase pqse: toward a deeper molecular understanding of virulence acquisition in pseudomonas aeruginosa |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769375/ https://www.ncbi.nlm.nih.gov/pubmed/24040042 http://dx.doi.org/10.1371/journal.pone.0073727 |
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