3QP2: Crystal Structure Of Cvir Ligand-Binding Domain Bound To C8-Hsl

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 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.
PDB ID: 3QP2Download
MMDB ID: 89570
PDB Deposition Date: 2011/2/11
Updated in MMDB: 2011/05
Experimental Method:
x-ray diffraction
Resolution: 1.64  Å
Source Organism:
Similar Structures:
Biological Unit for 3QP2: dimeric; determined by author and by software (PISA)
Molecular Components in 3QP2
Label Count Molecule
Proteins (2 molecules)
Cvir Transcriptional Regulator
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB