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A Strategy for Antagonizing Quorum Sensing
Open accessAbstract
SUMMARY 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 multi-domain proteins.
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PHENIX : building new software for automated crystallographic structure determination
Adams, P. D., Grosse-Kunstleve, R. W., Hung, L.-W., Ioerger, T. R., McCoy, A. J., Moriarty, N. W., Read, R. J., Sacchettini, J. C., Sauter, N. K., & Terwilliger, T. C. (2002) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444902016657 · Cited by 4,361
Cited by
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Yan, D., Li, Y., Liu, Y., Li, N., Zhang, X., & Yan, C. (2021) · Molecules · doi:10.3390/molecules26237136 · Cited by 608
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Paczkowski, J. E., Mukherjee, S., McCready, A. R., Cong, J.-P., Aquino, C. J., Kim, H., Henke, B. R., Smith, C. D., & Bassler, B. L. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.770552 · Cited by 319
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Metadata
- Authors
- Chen, G., Swem, L. R., Swem, D. L., Stauff, D. L., O'Loughlin, C. T., Jeffrey, P. D., Bassler, B. L., & Hughson, F. M.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 42
- Issue
- 2
- Pages
- 199-209
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1977541245
- Cited by
- 312
- References
- 4
- FWCI
- 7.64
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Chen, G., Swem, L. R., Swem, D. L., Stauff, D. L., O'Loughlin, C. T., Jeffrey, P. D., Bassler, B. L., & Hughson, F. M. (2011). A Strategy for Antagonizing Quorum Sensing. Molecular Cell. https://doi.org/10.1016/j.molcel.2011.04.003
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