ArticleBiophysical journal2010
Anesthetic binding in a pentameric ligand-gated ion channel: GLIC.
Article in Biophysical journal, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 45 citations in OpenAlex.
- General anesthetic modulation of a pentameric ligand-gated ion channel explored with simulations.Biophysical journal · 2026Article
- Druggable Lipid Binding Sites in Pentameric Ligand-Gated Ion Channels and Transient Receptor Potential Channels.Frontiers in physiology · 2021Review
- Mutagenesis computer experiments in pentameric ligand-gated ion channels: the role of simulation tools with different resolution.Interface focus · 2019Review
- Propofol inhibits the voltage-gated sodium channel NaChBac at multiple sites.The Journal of general physiology · 2018Article
- Mapping two neurosteroid-modulatory sites in the prototypic pentameric ligand-gated ion channel GLIC.The Journal of biological chemistry · 2018Article
- Recent progress on the molecular pharmacology of propofol.F1000Research · 2018Review
- A chimeric prokaryotic-eukaryotic pentameric ligand gated ion channel reveals interactions between the extracellular and transmembrane domains shape neurosteroid modulation.Neuropharmacology · 2017Article
- Ketamine Inhibition of the Pentameric Ligand-Gated Ion Channel GLIC.Biophysical journal · 2017Article
- GABA-ρ receptors: distinctive functions and molecular pharmacology.British journal of pharmacology · 2017Review
- Common Anesthetic-binding Site for Inhibition of Pentameric Ligand-gated Ion Channels.Anesthesiology · 2016Article
- Common Internal Allosteric Network Links Anesthetic Binding Sites in a Pentameric Ligand-Gated Ion Channel.PloS one · 2016Article
- Direct Pore Binding as a Mechanism for Isoflurane Inhibition of the Pentameric Ligand-gated Ion Channel ELIC.Scientific reports · 2015Article
- Atomistic insights into human Cys-loop receptors by solution NMR.Biochimica et biophysica acta · 2015Article
- The molecular pharmacology of volatile anesthetics.International anesthesiology clinics · 2015Review
- Hydrocarbon molar water solubility predicts NMDA vs. GABAA receptor modulation.BMC pharmacology & toxicology · 2014Article
- A predicted binding site for cholesterol on the GABAA receptor.Biophysical journal · 2014Article
- Photoaffinity labeling the propofol binding site in GLIC.Biochemistry · 2014Article
- Seeking structural specificity: direct modulation of pentameric ligand-gated ion channels by alcohols and general anesthetics.Pharmacological reviews · 2014Review
- Insights into distinct modulation of α7 and α7β2 nicotinic acetylcholine receptors by the volatile anesthetic isoflurane.The Journal of biological chemistry · 2013Article
- Inhibition versus potentiation of ligand-gated ion channels can be altered by a single mutation that moves ligands between intra- and intersubunit sites.Structure (London, England : 1993) · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cys-loop receptors are molecular targets of general anesthetics, but the knowledge of anesthetic binding to these proteins remains limited. Here we investigate anesthetic binding to the bacterial Gloeobacter violaceus pentameric ligand-gated ion channel (GLIC), a structural homolog of cys-loop receptors, using an experimental and computational hybrid approach. Tryptophan fluorescence quenching experiments showed halothane and thiopental binding at three tryptophan-associated sites in the extracellular (EC) domain, transmembrane (TM) domain, and EC-TM interface of GLIC. An additional binding site at the EC-TM interface was predicted by docking analysis and validated by quenching experiments on the N200W GLIC mutant. The binding affinities (K(D)) of 2.3 ± 0.1 mM and 0.10 ± 0.01 mM were derived from the fluorescence quenching data of halothane and thiopental, respectively. Docking these anesthetics to the original GLIC crystal structure and the structures relaxed by molecular dynamics simulations revealed intrasubunit sites for most halothane binding and intersubunit sites for thiopental binding. Tryptophans were within reach of both intra- and intersubunit binding sites. Multiple molecular dynamics simulations on GLIC in the presence of halothane at different sites suggested that anesthetic binding at the EC-TM interface disrupted the critical interactions for channel gating, altered motion of the TM23 linker, and destabilized the open-channel conformation that can lead to inhibition of GLIC channel current. The study has not only provided insights into anesthetic binding in GLIC, but also demonstrated a successful fusion of experiments and computations for understanding anesthetic actions in complex proteins.
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Registered trials
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.