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Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10630-5. Epub 2006 Jun 30.

Discrete steps in sensing of beta-lactam antibiotics by the BlaR1 protein of the methicillin-resistant Staphylococcus aureus bacterium.

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  • 1School of Biosciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.

Abstract

Chemical sensing by cell-surface receptors to effect signal transduction is a ubiquitous biological event. Despite extensive structural biochemical study, detailed knowledge of how signal transduction occurs is largely lacking. We report herein a kinetic and structural study, obtained by stopped-flow IR spectroscopy, of the activation of the BlaR1 receptor of the Staphylococcus aureus bacterium by beta-lactam antibiotics. The cell-surface BlaR1 receptor alerts the bacterium to the presence of beta-lactam antibiotics, resulting in expression of the gene for a beta-lactamase enzyme. This enzyme hydrolytically destroys the remaining beta-lactam antibiotics. IR spectroscopic interrogation of the beta-lactam-BlaR1 receptor reaction has allowed the simultaneous measurement of the chemical events of receptor recognition of the beta-lactam and the characterization of the conformational changes in the BlaR1 receptor that result. The key chemical events in beta-lactam recognition are serine acylation and subsequent irreversible decarboxylation of the BlaR1 active site lysine carbamate. Both events are observed by stopped-flow IR kinetics and (13)C isotope-edited IR spectroscopy. The secondary structural changes in the BlaR1 receptor conformation that occur as a consequence of this acylation/decarboxylation are predicted to correlate to the signal transduction event accomplished by this receptor.

PMID:
16815972
[PubMed - indexed for MEDLINE]
PMCID:
PMC1502283
Free PMC Article
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