Structural highlights
Publication Abstract from PubMedQuorum-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 approximately 60 A, twice the approximately 30 A separation required for operator binding. This approach may represent a general strategy for the inhibition of multidomain proteins. A strategy for antagonizing quorum sensing.,Chen G, Swem LR, Swem DL, Stauff DL, O'Loughlin CT, Jeffrey PD, Bassler BL, Hughson FM Mol Cell. 2011 Apr 22;42(2):199-209. PMID:21504831[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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