Issue 30, 2017
From the journal:

Organic & Biomolecular Chemistry

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

Alexander G. Ekström,a   Van Kelly,a   Jon Marles-Wright, ORCID logo b   Scott L. Cockroft ORCID logo a  and  Dominic J. Campopiano ORCID logo *a  

* Corresponding authors

a EaStCHEM School of Chemistry, University of Edinburgh, Joseph Black Building, David Brewster Road, Edinburgh, UK
E-mail: Dominic.Campopiano@ed.ac.uk

b School of Biological Science, Newcastle University, Devonshire Building, Newcastle upon Tyne, UK

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)

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Article information

DOI
https://doi.org/10.1039/C7OB01396E
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

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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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