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...

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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
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author Ekström, Alexander G.
Kelly, Van
Marles-Wright, Jon
Cockroft, Scott L.
Campopiano, Dominic J.
author_facet Ekström, Alexander G.
Kelly, Van
Marles-Wright, Jon
Cockroft, Scott L.
Campopiano, Dominic J.
author_sort Ekström, Alexander G.
collection PubMed
description 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.
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spelling pubmed-57083392018-01-05 Structural evidence for the covalent modification of FabH by 4,5-dichloro-1,2-dithiol-3-one (HR45) Ekström, Alexander G. Kelly, Van Marles-Wright, Jon Cockroft, Scott L. Campopiano, Dominic J. Org Biomol Chem Chemistry 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. Royal Society of Chemistry 2017-08-14 2017-07-17 /pmc/articles/PMC5708339/ /pubmed/28715001 http://dx.doi.org/10.1039/c7ob01396e Text en This journal is © The Royal Society of Chemistry 2017 http://creativecommons.org/licenses/by/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence (CC BY 3.0)
spellingShingle Chemistry
Ekström, Alexander G.
Kelly, Van
Marles-Wright, Jon
Cockroft, Scott L.
Campopiano, Dominic J.
Structural evidence for the covalent modification of FabH by 4,5-dichloro-1,2-dithiol-3-one (HR45)
title Structural evidence for the covalent modification of FabH by 4,5-dichloro-1,2-dithiol-3-one (HR45)
title_full Structural evidence for the covalent modification of FabH by 4,5-dichloro-1,2-dithiol-3-one (HR45)
title_fullStr Structural evidence for the covalent modification of FabH by 4,5-dichloro-1,2-dithiol-3-one (HR45)
title_full_unstemmed Structural evidence for the covalent modification of FabH by 4,5-dichloro-1,2-dithiol-3-one (HR45)
title_short Structural evidence for the covalent modification of FabH by 4,5-dichloro-1,2-dithiol-3-one (HR45)
title_sort structural evidence for the covalent modification of fabh by 4,5-dichloro-1,2-dithiol-3-one (hr45)
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5708339/
https://www.ncbi.nlm.nih.gov/pubmed/28715001
http://dx.doi.org/10.1039/c7ob01396e
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