5X3R

Crystal structure of the SmcR complexed with QStatin

Summary for 5X3R

• Entry DOI: 10.2210/pdb5x3r/pdb
• Descriptor: LuxR family transcriptional regulator, 1-(5-bromanylthiophen-2-yl)sulfonylpyrazole, SULFATE ION, ... (4 entities in total)
• Functional Keywords: quorum sensing inhibitor, dna binding protein
• Biological source: Vibrio vulnificus
• Total number of polymer chains: 4
• Total formula weight: 97286.64

Authors

Jang, S.Y.,Hwang, J.,Kim, M.H. (deposition date: 2017-02-07, release date: 2018-01-24, Last modification date: 2023-11-22)

Primary citation

Kim, B.S.,Jang, S.Y.,Bang, Y.J.,Hwang, J.,Koo, Y.,Jang, K.K.,Lim, D.,Kim, M.H.,Choi, S.H.
QStatin, a Selective Inhibitor of Quorum Sensing inVibrioSpecies
MBio, 9:-, 2018

PubMed Abstract: Pathogenic species cause diseases in diverse marine animals reared in aquaculture. Since their pathogenesis, persistence, and survival in marine environments are regulated by quorum sensing (QS), QS interference has attracted attention as a means to control these bacteria in aquatic settings. A few QS inhibitors of species have been reported, but detailed molecular mechanisms are lacking. Here, we identified a novel, potent, and selective QS inhibitor, named QStatin [1-(5-bromothiophene-2-sulfonyl)-1H-pyrazole], which affects LuxR homologues, the well-conserved master transcriptional regulators for QS in species. Crystallographic and biochemical analyses showed that QStatin binds tightly to a putative ligand-binding pocket in SmcR, the LuxR homologue in , and changes the flexibility of the protein, thereby altering its transcription regulatory activity. Transcriptome analysis revealed that QStatin results in SmcR dysfunction, affecting the expression of SmcR regulon required for virulence, motility/chemotaxis, and biofilm dynamics. Notably, QStatin attenuated representative QS-regulated phenotypes in various species, including virulence against the brine shrimp (). Together, these results provide molecular insights into the mechanism of action of an effective, sustainable QS inhibitor that is less susceptible to resistance than other antimicrobial agents and useful in controlling the virulence of species in aquacultures. Yields of aquaculture, such as penaeid shrimp hatcheries, are greatly affected by vibriosis, a disease caused by pathogenic infections. Since bacterial cell-to-cell communication, known as quorum sensing (QS), regulates pathogenesis of species in marine environments, QS inhibitors have attracted attention as alternatives to conventional antibiotics in aquatic settings. Here, we used target-based high-throughput screening to identify QStatin, a potent and selective inhibitor of LuxR homologues, which are well-conserved master QS regulators in species. Structural and biochemical analyses revealed that QStatin binds tightly to a putative ligand-binding pocket on SmcR, the LuxR homologue in , and affects expression of QS-regulated genes. Remarkably, QStatin attenuated diverse QS-regulated phenotypes in various species, including pathogenesis against brine shrimp, with no impact on bacterial viability. Taken together, the results suggest that QStatin may be a sustainable antivibriosis agent useful in aquacultures.

PubMed: 29382732
DOI: 10.1128/mBio.02262-17

Experimental method

X-RAY DIFFRACTION (2.1 Å)