A strategy for antagonizing quorum sensing.
| Autor: | Chen G; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA., Swem LR, Swem DL, Stauff DL, O'Loughlin CT, Jeffrey PD, Bassler BL, Hughson FM |
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| Jazyk: | angličtina |
| Zdroj: | Molecular cell [Mol Cell] 2011 Apr 22; Vol. 42 (2), pp. 199-209. |
| DOI: | 10.1016/j.molcel.2011.04.003 |
| Abstrakt: | Quorum-sensing bacteria communicate via small molecules called autoinducers to coordinate collective behaviors. Because quorum sensing controls virulence factor expression in many clinically relevant pathogens, membrane-permeable quorum sensing antagonists that prevent population-wide expression of virulence genes offer a potential route to novel antibacterial therapeutics. Here, we report a strategy for inhibiting quorum-sensing receptors of the widespread LuxR family. Structure-function studies with natural and synthetic ligands demonstrate that the dimeric LuxR-type transcription factor CviR from Chromobacterium violaceum is potently antagonized by molecules that bind in place of the native acylated homoserine lactone autoinducer, provided that they stabilize a closed conformation. In such conformations, each of the two DNA-binding domains interacts with the ligand-binding domain of the opposing monomer. Consequently, the DNA-binding helices are held apart by ∼60 Å, twice the ∼30 Å separation required for operator binding. This approach may represent a general strategy for the inhibition of multidomain proteins. (Copyright © 2011 Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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