ArticleOrganic & biomolecular chemistry2015
Unraveling the contributions of hydrogen-bonding interactions to the activity of native and non-native ligands in the quorum-sensing receptor LasR.
Article in Organic & biomolecular chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Traditional Chinese Medicine Monomer Bakuchiol Attenuates the Pathogenicity ofInternational journal of molecular sciences · 2024Article
- 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
- Investigation of bioactive components responsible for the antibacterial and anti-biofilm activities ofRSC advances · 2024Article
- Characterization of natural product inhibitors of quorum sensing inbioRxiv : the preprint server for biology · 2024Article
- Design and synthesis of quorum-sensing agonist for improving biofilm formation and the application ofFrontiers in microbiology · 2024Article
- Characterization and Mechanism of Tea Polyphenols Inhibiting Biogenic Amine Accumulation in Marinated Spanish Mackerel.Foods (Basel, Switzerland) · 2023Article
- Inhibitory effect and underlying mechanism of cinnamon and clove essential oils onFrontiers in microbiology · 2023Article
- Article
- Design, Synthesis, and Biochemical Characterization of Non-Native Antagonists of theACS infectious diseases · 2020Article
- An Autoinducer Analogue Reveals an Alternative Mode of Ligand Binding for the LasR Quorum-Sensing Receptor.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
- Design and Synthesis of Lactams Derived from Mucochloric and Mucobromic Acids asMolecules (Basel, Switzerland) · 2018Article
- Reducing Quorum Sensing-Mediated Virulence Factor Expression and Biofilm Formation inFrontiers in microbiology · 2018Article
- Molecular Insights into the Impact of Oxidative Stress on the Quorum-Sensing Regulator Protein LasR.The Journal of biological chemistry · 2016Article
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Authors and funding
4 authors.
Funding
Abstract
Quorum sensing (QS) via the synthesis and detection of N-acyl L-homoserine lactone (AHL) signals regulates important pathogenic and mutualistic phenotypes in many bacteria. Over the past two decades, the development of non-native molecules that modulate this cell-cell signaling process has become an active area of research. The majority of these compounds were designed to block binding of the native AHL signal to its cognate LuxR-type receptor, and much effort has focused on LasR in the opportunistic pathogen Pseudomonas aeruginosa. Despite a small set of reported LasR structural data, it remains unclear which polar interactions are most important for either (i) activation of the LasR receptor by its native AHL signal, N-(3-oxo)-dodecanoyl L-homoserine lactone (OdDHL), or (ii) activation or inhibition of LasR by related AHL analogs. Herein, we report our investigations into the activity of OdDHL and five synthetic analogs in wild-type LasR and in nine LasR mutants with modifications to key polar residues in their ligand binding sites. Our results allowed us to rank, for the first time, the relative importance of each LasR:OdDHL hydrogen bond for LasR activation and provide strong evidence for the five synthetic ligands binding LasR in a very similar orientation as OdDHL. By delineating the specific molecular interactions that are important for LasR modulation by AHLs, these findings should aid in the design of new synthetic modulators of LasR (and homologous LuxR-type receptors) with improved potencies and selectivities.
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