ArticleChemistry & biology2014
Mutational analysis of the quorum-sensing receptor LasR reveals interactions that govern activation and inhibition by nonlactone ligands.
Article in Chemistry & biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 46 citations in OpenAlex.
- Insights into the Mechanisms of Small Molecule-Induced Agonism and Antagonism of a Quorum Sensing Receptor inJournal of the American Chemical Society · 2025Article
- Characterization of natural product inhibitors of quorum sensing reveals competitive inhibition ofMicrobiology spectrum · 2024Article
- Abiotic Small Molecule Inhibitors and Activators of the LasR Quorum Sensing Receptor inACS infectious diseases · 2024Article
- Characterization of natural product inhibitors of quorum sensing inbioRxiv : the preprint server for biology · 2024Article
- A data-driven machine learning approach for discovering potent LasR inhibitors.Bioengineered · 2023Article
- ModifiedFrontiers in molecular biosciences · 2023Article
- Autoinducer-fluorophore conjugates enable FRET in LuxR proteins in vitro and in cells.Nature chemical biology · 2022Article
- Resistance Is Not Futile: The Role of Quorum Sensing Plasticity inMicroorganisms · 2022Review
- A novel phenolic derivative inhibits AHL-dependent quorum sensing signaling inFrontiers in pharmacology · 2022Article
- Inhibitory Effects of Artificial Sweeteners on Bacterial Quorum Sensing.International journal of molecular sciences · 2021Article
- Growing emergence of drug-resistantIranian journal of basic medical sciences · 2021Review
- Assessing the Molecular Targets and Mode of Action of Furanone C-30 onMolecules (Basel, Switzerland) · 2021Article
- Molecular simulations of lipid membrane partitioning and translocation by bacterial quorum sensing modulators.PloS one · 2021Article
- Bacterial Quorum Sensing Signals Self-Assemble in Aqueous Media to Form Micelles and Vesicles: An Integrated Experimental and Molecular Dynamics Study.The journal of physical chemistry. B · 2020Article
- Design, Synthesis, and Biochemical Characterization of Non-Native Antagonists of theACS infectious diseases · 2020Article
- Adapting to the Airways: Metabolic Requirements ofMetabolites · 2019Review
- An autoinducer-independent RhlR quorum-sensing receptor enables analysis of RhlR regulation.PLoS pathogens · 2019Article
- An Autoinducer Analogue Reveals an Alternative Mode of Ligand Binding for the LasR Quorum-Sensing Receptor.ACS chemical biology · 2019Article
- N-Acyl l-Homocysteine Thiolactones Are Potent and Stable Synthetic Modulators of the RhlR Quorum Sensing Receptor in Pseudomonas aeruginosa.ACS chemical biology · 2019Article
- Structural determinants driving homoserine lactone ligand selection in theProceedings of the National Academy of Sciences of the United States of America · 2019Article
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5 authors at 2 institutions in 1 country.
Funding
Abstract
Gram-negative bacteria use N-acyl L-homoserine lactone (AHL) quorum-sensing (QS) signals to regulate the expression of myriad phenotypes. Non-native AHL analogs can strongly attenuate QS receptor activity and thereby QS signaling; however, we currently lack a molecular understanding of the mechanisms by which most of these compounds elicit their agonistic or antagonistic profiles. In this study, we investigated the origins of striking activity profile switches (i.e., receptor activator to inhibitor, and vice versa) observed upon alteration of the lactone head group in certain AHL analogs. Reporter gene assays of mutant versions of the Pseudomonas aeruginosa QS receptor LasR revealed that interactions between the ligands and Trp60, Tyr56, and Ser129 govern whether these ligands behave as LasR activators or inhibitors. Using this knowledge, we propose a model for the modulation of LasR by AHL analogs-encompassing a subtly different interaction with the binding pocket to a global change in LasR conformation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.