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

Alexander G. Ekström, Van Kelly, Jon Marles-wright, Scott L. Cockroft, Dominic J. Campopiano

Research output: Contribution to journalArticlepeer-review

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 b-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.
Original languageEnglish
Pages (from-to)6310-6313
JournalOrganic & Biomolecular chemistry
Volume15
Issue number30
Early online date17 Jul 2017
DOIs
Publication statusE-pub ahead of print - 17 Jul 2017

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