@article{86956,
  keywords = {Models, Molecular, Protein Conformation, DNA, Crystallography, X-Ray, Mutation, Biofilms, Anti-Bacterial Agents, Dose-Response Relationship, Drug, Molecular Structure, Structure-Activity Relationship, Quorum Sensing, 4-Butyrolactone, Binding Sites, Repressor Proteins, Trans-Activators, Lactones, Virulence, Ligands, Chromobacterium},
  author = {Guozhou Chen and Lee Swem and Danielle Swem and Devin Stauff and Colleen O{\textquoteright}Loughlin and Philip Jeffrey and Bonnie Bassler and Frederick Hughson},
  title = {A strategy for antagonizing quorum sensing.},
  abstract = {<p>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 {\r A}, twice the \~{}30 {\r A} separation required for operator binding. This approach may represent a general strategy for the inhibition of multidomain proteins.</p>
},
  year = {2011},
  journal = {Mol Cell},
  volume = {42},
  pages = {199-209},
  month = {04/2011},
  issn = {1097-4164},
  doi = {10.1016/j.molcel.2011.04.003},
  language = {eng},
}