Exploring the mode of action of inhibitors targeting the PhoP response regulator of Salmonella enterica through comprehensive pharmacophore approaches

The PhoQ/PhoP two-component system regulates the physiological and virulence functions of Salmonella enterica. However, the mode of action of known PhoP inhibitors is unclear. We systematically constructed a pharmacophore model of inhibitors to probe the interface pharmacophore model of the PhoP dim...

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Autores principales: Tsai, Keng-Chang, Hung, Po-Pin, Cheng, Ching-Feng, Chen, Chinpan, Tseng, Tien-Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2019
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9062048/
https://www.ncbi.nlm.nih.gov/pubmed/35517705
http://dx.doi.org/10.1039/c9ra00620f
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author Tsai, Keng-Chang
Hung, Po-Pin
Cheng, Ching-Feng
Chen, Chinpan
Tseng, Tien-Sheng
author_facet Tsai, Keng-Chang
Hung, Po-Pin
Cheng, Ching-Feng
Chen, Chinpan
Tseng, Tien-Sheng
author_sort Tsai, Keng-Chang
collection PubMed
description The PhoQ/PhoP two-component system regulates the physiological and virulence functions of Salmonella enterica. However, the mode of action of known PhoP inhibitors is unclear. We systematically constructed a pharmacophore model of inhibitors to probe the interface pharmacophore model of the PhoP dimer, coupling it with Ligplot analysis. We found that these inhibitors bind on the α5-helix, altering the conformation and interfering with PhoP binding on DNA.
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spelling pubmed-90620482022-05-04 Exploring the mode of action of inhibitors targeting the PhoP response regulator of Salmonella enterica through comprehensive pharmacophore approaches Tsai, Keng-Chang Hung, Po-Pin Cheng, Ching-Feng Chen, Chinpan Tseng, Tien-Sheng RSC Adv Chemistry The PhoQ/PhoP two-component system regulates the physiological and virulence functions of Salmonella enterica. However, the mode of action of known PhoP inhibitors is unclear. We systematically constructed a pharmacophore model of inhibitors to probe the interface pharmacophore model of the PhoP dimer, coupling it with Ligplot analysis. We found that these inhibitors bind on the α5-helix, altering the conformation and interfering with PhoP binding on DNA. The Royal Society of Chemistry 2019-03-21 /pmc/articles/PMC9062048/ /pubmed/35517705 http://dx.doi.org/10.1039/c9ra00620f Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Tsai, Keng-Chang
Hung, Po-Pin
Cheng, Ching-Feng
Chen, Chinpan
Tseng, Tien-Sheng
Exploring the mode of action of inhibitors targeting the PhoP response regulator of Salmonella enterica through comprehensive pharmacophore approaches
title Exploring the mode of action of inhibitors targeting the PhoP response regulator of Salmonella enterica through comprehensive pharmacophore approaches
title_full Exploring the mode of action of inhibitors targeting the PhoP response regulator of Salmonella enterica through comprehensive pharmacophore approaches
title_fullStr Exploring the mode of action of inhibitors targeting the PhoP response regulator of Salmonella enterica through comprehensive pharmacophore approaches
title_full_unstemmed Exploring the mode of action of inhibitors targeting the PhoP response regulator of Salmonella enterica through comprehensive pharmacophore approaches
title_short Exploring the mode of action of inhibitors targeting the PhoP response regulator of Salmonella enterica through comprehensive pharmacophore approaches
title_sort exploring the mode of action of inhibitors targeting the phop response regulator of salmonella enterica through comprehensive pharmacophore approaches
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9062048/
https://www.ncbi.nlm.nih.gov/pubmed/35517705
http://dx.doi.org/10.1039/c9ra00620f
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