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

Lookup NU author(s): Dr Jon Marles-Wright

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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.


Publication metadata

Author(s): Wallock-Richards DJ, Marles-Wright J, Clarke DJ, Maitra A, Dodds M, Hanley B, Campopiano DJ

Publication type: Article

Publication status: Published

Journal: Chemical Communications

Year: 2015

Volume: 51

Issue: 52

Pages: 10483-10485

Print publication date: 04/07/2015

Online publication date: 18/05/2015

Acceptance date: 12/05/2015

Date deposited: 13/06/2016

ISSN (print): 1359-7345

ISSN (electronic): 1364-548X

Publisher: Royal Society of Chemistry

URL: http://dx.doi.org/10.1039/C5CC01816A

DOI: 10.1039/C5CC01816A

PubMed id: 26029850


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