Issue 30, 2017

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 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.

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

Supplementary files

Article information

Article type
Communication
Submitted
08 Jun 2017
Accepted
05 Jul 2017
First published
17 Jul 2017
This article is Open Access
Creative Commons BY license

Org. Biomol. Chem., 2017,15, 6310-6313

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

A. G. Ekström, V. Kelly, J. Marles-Wright, S. L. Cockroft and D. J. Campopiano, Org. Biomol. Chem., 2017, 15, 6310 DOI: 10.1039/C7OB01396E

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