Structural evidence for the covalent modification of FabH by 4,5-dichloro-1,2-dithiol-3-one (HR45)-Reference-Cited by-同舟云学术

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

Published:2017 Issue:30 Volume:15 Page:6310-6313
ISSN:1477-0520
Container-title:Organic & Biomolecular Chemistry
language:en
Short-container-title:Org. Biomol. Chem.

Author:

Ekström Alexander G.¹²³⁴,Kelly Van¹²³⁴,Marles-Wright Jon⁵⁶⁷⁴^ORCID,Cockroft Scott L.¹²³⁴^ORCID,Campopiano Dominic J.¹²³⁴^ORCID

Affiliation:

1. EaStCHEM School of Chemistry

2. University of Edinburgh

3. Edinburgh

4. UK

5. School of Biological Science

6. Newcastle University

7. Newcastle upon Tyne

Abstract

Mass spectrometry and modelling shows the 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.

Funder

Engineering and Physical Sciences Research Council

Biotechnology and Biological Sciences Research Council

Publisher

Royal Society of Chemistry (RSC)

Subject

Organic Chemistry,Physical and Theoretical Chemistry,Biochemistry

Link

http://pubs.rsc.org/en/content/articlepdf/2017/OB/C7OB01396E

Reference32 articles.

1. Bacterial Fatty Acid Biosynthesis: Targets for Antibacterial Drug Discovery

2. Purification, Characterization, and Identification of Novel Inhibitors of the β-Ketoacyl-Acyl Carrier Protein Synthase III (FabH) from Staphylococcus aureus