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

ABSTRACT: 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 ?-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.

SUBMITTER: Ekstrom AG

PROVIDER: S-EPMC5708339 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Ekström Alexander G AG Kelly Van V Marles-Wright Jon J Cockroft Scott L SL Campopiano Dominic J DJ

Organic & biomolecular chemistry 20170801 30

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. ...[more]

PMID: 28715001

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