3QP6

Crystal structure of CviR (Chromobacterium violaceum 12472) bound to C6-HSL

Summary for 3QP6

• Entry DOI: 10.2210/pdb3qp6/pdb
• Related: 3QP1 3QP2 3QP4 3QP5 3QP7 3QP8
• Descriptor: CviR transcriptional regulator, N-[(3S)-2-oxotetrahydrofuran-3-yl]hexanamide (3 entities in total)
• Functional Keywords: quorum sensing, agonist, antagonist, luxr, acylated homoserine lactone, transcription factor, dna binding protein, ligand binding domain, signal receptor, n-hexanoyl-l-homoserine lactone, transcription
• Biological source: Chromobacterium violaceum
• Total number of polymer chains: 1
• Total formula weight: 29760.01

Authors

Chen, G.,Swem, L.,Swem, D.,Stauff, D.,O'Loughlin, C.,Jeffrey, P.,Bassler, B.,Hughson, F. (deposition date: 2011-02-11, release date: 2011-03-30, Last modification date: 2023-09-13)

Primary citation

Chen, G.,Swem, L.R.,Swem, D.L.,Stauff, D.L.,O'Loughlin, C.T.,Jeffrey, P.D.,Bassler, B.L.,Hughson, F.M.
A strategy for antagonizing quorum sensing.
Mol.Cell, 42:199-209, 2011

PubMed Abstract: 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.

PubMed: 21504831
DOI: 10.1016/j.molcel.2011.04.003

Experimental method

X-RAY DIFFRACTION (2 Å)