Structural evidence for the covalent modification of FabH by 4,5-dichloro-1,2-dithiol-3-one (HR45)

We use mass spectrometry analysis and molecular modelling to show the established antimicrobial inhibitor 4,5-dichloro-1,2-dithiol-3-one (HR45) acts by forming a covalent adduct with the target β-ketoacyl-ACP synthase III (FabH). The 5-chloro substituent directs attack of the essential active site t...

Descripción completa

Detalles Bibliográficos
Autores principales: Ekström, Alexander G., Kelly, Van, Marles-Wright, Jon, Cockroft, Scott L., Campopiano, Dominic J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2017
Materias:
Chemistry
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5708339/
https://www.ncbi.nlm.nih.gov/pubmed/28715001
http://dx.doi.org/10.1039/c7ob01396e
Descripción
Sumario:We use mass spectrometry analysis and molecular modelling to show the established antimicrobial inhibitor 4,5-dichloro-1,2-dithiol-3-one (HR45) acts by forming a covalent adduct with the target β-ketoacyl-ACP synthase III (FabH). The 5-chloro substituent directs attack of the essential active site thiol (C112) via a Michael-type addition elimination reaction mechanism.

Ejemplares similares