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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Detalles Bibliográficos
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
Descripción
Sumario: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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