ArticleThe Journal of biological chemistry2013
Multisite binding of a general anesthetic to the prokaryotic pentameric Erwinia chrysanthemi ligand-gated ion channel (ELIC).
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 94 citations in OpenAlex.
- Sevoflurane inhibition of the developmentally expressed neuronal sodium channel NaScientific reports · 2025Article
- Alchemical Free Energy Calculations on Membrane-Associated Proteins.Journal of chemical theory and computation · 2023Review
- General anesthesia bullies the gut: a toxic relationship with dysbiosis and cognitive dysfunction.Psychopharmacology · 2022Review
- Polyunsaturated fatty acids inhibit a pentameric ligand-gated ion channel through one of two binding sites.eLife · 2022Article
- Druggable Lipid Binding Sites in Pentameric Ligand-Gated Ion Channels and Transient Receptor Potential Channels.Frontiers in physiology · 2021Review
- Modulation of theeLife · 2020Article
- Triple arginines as molecular determinants for pentameric assembly of the intracellular domain of 5-HTThe Journal of general physiology · 2019Article
- Towards a Comprehensive Understanding of Anesthetic Mechanisms of Action: A Decade of Discovery.Trends in pharmacological sciences · 2019Review
- Differential Inhibition of Neuronal Sodium Channel Subtypes by the General Anesthetic Isoflurane.The Journal of pharmacology and experimental therapeutics · 2019Article
- Electrostatics, proton sensor, and networks governing the gating transition in GLIC, a proton-gated pentameric ion channel.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Allosteric potentiation of a ligand-gated ion channel is mediated by access to a deep membrane-facing cavity.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Crystal structures of a pentameric ion channel gated by alkaline pH show a widely open pore and identify a cavity for modulation.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Permeating disciplines: Overcoming barriers between molecular simulations and classical structure-function approaches in biological ion transport.Biochimica et biophysica acta. Biomembranes · 2018Review
- An allosteric binding site of the α7 nicotinic acetylcholine receptor revealed in a humanized acetylcholine-binding protein.The Journal of biological chemistry · 2018Article
- Alphaxalone Binds in Inner Transmembrane β+-α- Interfaces of α1β3γ2 γ-Aminobutyric Acid Type A Receptors.Anesthesiology · 2018Article
- X-Ray Crystallographic Studies for Revealing Binding Sites of General Anesthetics in Pentameric Ligand-Gated Ion Channels.Methods in enzymology · 2018Article
- Combining Mutations and Electrophysiology to Map Anesthetic Sites on Ligand-Gated Ion Channels.Methods in enzymology · 2018Review
- Recent progress on the molecular pharmacology of propofol.F1000Research · 2018Review
- Solution NMR Studies of Anesthetic Interactions with Ion Channels.Methods in enzymology · 2018Article
- A chimeric prokaryotic-eukaryotic pentameric ligand gated ion channel reveals interactions between the extracellular and transmembrane domains shape neurosteroid modulation.Neuropharmacology · 2017Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 4 countries.
Funding
Abstract
Pentameric ligand-gated ion channels (pLGICs), such as nicotinic acetylcholine, glycine, γ-aminobutyric acid GABA(A/C) receptors, and the Gloeobacter violaceus ligand-gated ion channel (GLIC), are receptors that contain multiple allosteric binding sites for a variety of therapeutics, including general anesthetics. Here, we report the x-ray crystal structure of the Erwinia chrysanthemi ligand-gated ion channel (ELIC) in complex with a derivative of chloroform, which reveals important features of anesthetic recognition, involving multiple binding at three different sites. One site is located in the channel pore and equates with a noncompetitive inhibitor site found in many pLGICs. A second transmembrane site is novel and is located in the lower part of the transmembrane domain, at an interface formed between adjacent subunits. A third site is also novel and is located in the extracellular domain in a hydrophobic pocket between the β7-β10 strands. Together, these results extend our understanding of pLGIC modulation and reveal several specific binding interactions that may contribute to modulator recognition, further substantiating a multisite model of allosteric modulation in this family of ion channels.
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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.