ArticleJournal of the American Chemical Society2013
Crystal structures of the LsrR proteins complexed with phospho-AI-2 and two signal-interrupting analogues reveal distinct mechanisms for ligand recognition.
Article in Journal of the American Chemical Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- New LsrK Ligands as AI-2 Quorum Sensing Interfering Compounds against Biofilm Formation.Journal of medicinal chemistry · 2024Article
- Structural characterization of two prototypical repressors of SorC family reveals tetrameric assemblies on DNA and mechanism of function.Nucleic acids research · 2024Article
- Neuromodulators as Interdomain Signaling Molecules Capable of Occupying Effector Binding Sites in Bacterial Transcription Factors.International journal of molecular sciences · 2023Article
- Structural Insights into the Ligand-LsrK Kinase Binding Mode: A Step Forward in the Discovery of Novel Antimicrobial Agents.Molecules (Basel, Switzerland) · 2023Article
- Antimicrobial Resistance and Recent Alternatives to Antibiotics for the Control of Bacterial Pathogens with an Emphasis on Foodborne Pathogens.Antibiotics (Basel, Switzerland) · 2023Review
- Mechanisms of Inhibition of Quorum Sensing as an Alternative for the Control ofMicroorganisms · 2022Review
- Tackling Antimicrobial Resistance with Small Molecules Targeting LsrK: Challenges and Opportunities.Journal of medicinal chemistry · 2020Article
- A Versatile Strategy for the Synthesis of 4,5-Dihydroxy-2,3-Pentanedione (DPD) and Related Compounds as Potential Modulators of Bacterial Quorum Sensing.Molecules (Basel, Switzerland) · 2018Article
- Evidence of link between quorum sensing and sugar metabolism inScience advances · 2018Article
- Increasing the soluble expression and crystallization of the Escherichia coli quorum-sensing protein LsrK.Acta crystallographica. Section F, Structural biology communications · 2017Article
- Glycation Reactivity of a Quorum-Sensing Signaling Molecule.Angewandte Chemie (International ed. in English) · 2016Article
- Directed assembly of a bacterial quorum.The ISME journal · 2016Article
- LsrF, a coenzyme A-dependent thiolase, catalyzes the terminal step in processing the quorum sensing signal autoinducer-2.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Review
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Quorum sensing (QS) is a cell-to-cell communication system responsible for a variety of bacterial phenotypes including virulence and biofilm formation. QS is mediated by small molecules, autoinducers (AIs), including AI-2 that is secreted by both Gram-positive and -negative microbes. LsrR is a key transcriptional regulator that governs the varied downstream processes by perceiving AI-2 signal, but its activation via autoinducer-binding remains poorly understood. Here, we provide detailed regulatory mechanism of LsrR from the crystal structures in complexes with the native signal (phospho-AI-2, D5P) and two quorum quenching antagonists (ribose-5-phosphate, R5P; phospho-isobutyl-AI-2, D8P). Interestingly, the bound D5P and D8P molecules are not the diketone forms but rather hydrated, and the hydrated moiety forms important H-bonds with the carboxylate of D243. The D5P-binding flipped out F124 of the binding pocket, and resulted in the disruption of the dimeric interface-1 by unfolding the α7 segment. However, the same movement of F124 by the D8P'-binding did not cause the unfolding of the α7 segment. Although the LsrR-binding affinity of R5P (Kd, ∼1 mM) is much lower than that of D5P and D8P (∼2.0 and ∼0.5 μM), the α-anomeric R5P molecule fits into the binding pocket without any structural perturbation, and thus stabilizes the LsrR tetramer. The binding of D5P, not D8P and R5P, disrupted the tetrameric structure and thus is able to activate LsrR. The detailed structural and mechanistic insights from this study could be useful for facilitating design of new antivirulence and antibiofilm agents based on LsrR.
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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.