Molecular basis of Streptococcus mutans sortase A inhibition by the flavonoid natural product trans-chalcone

Daynea J Wallock-Richards, Jon Marles-Wright, David J Clarke, Amarnath Maitra, Michael Dodds, Bryan Hanley, Dominic J Campopiano

Research output: Contribution to journalArticlepeer-review

Abstract

Sortase A (SrtA) from Gram positive pathogens is an attractive target for inhibitors due to its role in the attachment of surface proteins to the cell wall. We found that the plant natural product trans-chalcone inhibits Streptococcus mutans SrtA in vitro and also inhibited S. mutans biofilm formation. Mass spectrometry revealed that the trans-chalcone forms a Michael addition adduct with the active site cysteine. The X-ray crystal structure of the SrtA H139A mutant provided new insights into substrate recognition by the sortase family. Our study suggests that chalcone flavonoids have potential as sortase-specific oral biofilm inhibitors.

Original languageEnglish
Pages (from-to)10483-10485
JournalChemical Communications
Volume51
DOIs
Publication statusPublished - 1 Jun 2015

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