Lyon, G. J., Mayville, P., Muir, T. W., Novick, R. P. (2000) Rational design of a global inhibitor of the virulence response in Staphylococcus aureus, based in part on localization of the site of inhibition to the receptor-histidine kinase, AgrC. Proceedings of the National Academy of Sciences of the United States of America, 97 (24). pp. 13330-13335. ISSN 0027-8424
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Abstract
Two-component signaling systems involving receptor-histidine kinases are ubiquitous in bacteria and have been found in yeast and plants. These systems provide the major means by which bacteria communicate with each other and the outside world. Remarkably, very little is known concerning the extracellular ligands that presumably bind to receptor-histidine kinases to initiate signaling. The two-component agr signaling circuit in Staphylococcus aureus is one system where the ligands are known in chemical detail, thus opening the door for detailed structure-activity relationship studies. These ligands are short (8- to 9-aa) peptides containing a thiolactone structure, in which the alpha-carboxyl group of the C-terminal amino acid is linked to the sulfhydryl group of a cysteine, which is always the fifth amino acid from the C terminus of the peptide. One unique aspect of the agr system is that peptides that activate virulence expression in one group of S. aureus strains also inhibit virulence expression in other groups of S. aureus strains. Herein, it is demonstrated by switching the receptor-histidine kinase, AgrC, between strains of different agr specificity types, that intragroup activation and intergroup inhibition are both mediated by the same group-specific receptors. These results have facilitated the development of a global inhibitor of virulence in S. aureus, which consists of a truncated version of one of the naturally occurring thiolactone peptides.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Amino Acid Sequence Binding Sites Drug Design Enzyme Inhibitors Escherichia coli Kinetics Lactones Ligands Oligopeptides Plasmids Protein Kinase Inhibitors Protein Kinases Signal Transduction Staphylococcus aureus Structure-Activity Relationship Virulence |
| Subjects: | organism description > bacteria bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase |
| CSHL Authors: | |
| Communities: | CSHL labs > Lyon lab |
| Depositing User: | Matt Covey |
| Date: | 2000 |
| Date Deposited: | 10 Dec 2012 20:13 |
| Last Modified: | 10 Sep 2019 19:34 |
| PMCID: | PMC27224 |
| URI: | https://repository.cshl.edu/id/eprint/26279 |
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