3QP5

Crystal structure of CviR bound to antagonist chlorolactone (CL)

3QP5 の概要

• エントリーDOI: 10.2210/pdb3qp5/pdb
• 関連するPDBエントリー: 3QP1 3QP2 3QP4 3QP6 3QP7 3QP8
• 分子名称: CviR transcriptional regulator, 4-(4-chlorophenoxy)-N-[(3S)-2-oxotetrahydrofuran-3-yl]butanamide (2 entities in total)
• 機能のキーワード: quorum sensing, agonist, antagonist, luxr, acylated homoserine lactone, transcription factor, dna binding protein, ligand binding domain, signal receptor, quorum sensing transcription factor, chlorolactone (cl), transcription
• 由来する生物種: Chromobacterium violaceum
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 120203.01

構造登録者

Chen, G.,Swem, L.,Swem, D.,Stauff, D.,O'Loughlin, C.,Jeffrey, P.,Bassler, B.,Hughson, F. (登録日: 2011-02-11, 公開日: 2011-03-30, 最終更新日: 2023-09-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3.249 Å)