ArticleBiochemistry2014
Photoaffinity labeling the propofol binding site in GLIC.
Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- A propofol binding site in the voltage sensor domain mediates inhibition of HCN1 channel activity.Science advances · 2025Article
- Binding Sites and the Mechanism of Action of Propofol and a Photoreactive Analogue in Prokaryotic Voltage-Gated Sodium Channels.ACS chemical neuroscience · 2021Article
- Mechanistic basis of propofol-induced disruption of kinesin processivity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Towards a Comprehensive Understanding of Anesthetic Mechanisms of Action: A Decade of Discovery.Trends in pharmacological sciences · 2019Review
- Multiple functional neurosteroid binding sites on GABAA receptors.PLoS biology · 2019Article
- Propofol inhibits prokaryotic voltage-gated NaThe Journal of general physiology · 2018Article
- Comparison of αβδ and αβγ GABAPharmacological research · 2018Review
- 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
- Mapping two neurosteroid-modulatory sites in the prototypic pentameric ligand-gated ion channel GLIC.The Journal of biological chemistry · 2018Article
- Sites and Functional Consequence of Alkylphenol Anesthetic Binding to Kv1.2 Channels.Molecular neurobiology · 2018Article
- X-Ray Crystallographic Studies for Revealing Binding Sites of General Anesthetics in Pentameric Ligand-Gated Ion Channels.Methods in enzymology · 2018Article
- Recent progress on the molecular pharmacology of propofol.F1000Research · 2018Review
- Common general anesthetic propofol impairs kinesin processivity.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Barbiturates Bind in the GLIC Ion Channel Pore and Cause Inhibition by Stabilizing a Closed State.The Journal of biological chemistry · 2017Article
- Structural Basis of Alcohol Inhibition of the Pentameric Ligand-Gated Ion Channel ELIC.Structure (London, England : 1993) · 2017Article
- Shedding Light on Anesthetic Mechanisms: Application of Photoaffinity Ligands.Anesthesia and analgesia · 2016Review
- Common Anesthetic-binding Site for Inhibition of Pentameric Ligand-gated Ion Channels.Anesthesiology · 2016Article
- Direct Pore Binding as a Mechanism for Isoflurane Inhibition of the Pentameric Ligand-gated Ion Channel ELIC.Scientific reports · 2015Article
- Anesthetics target interfacial transmembrane sites in nicotinic acetylcholine receptors.Neuropharmacology · 2015Review
- Desformylflustrabromine (dFBr) and [3H]dFBr-Labeled Binding Sites in a Nicotinic Acetylcholine Receptor.Molecular pharmacology · 2015Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Propofol, an intravenous general anesthetic, produces many of its anesthetic effects in vivo by potentiating the responses of GABA type A receptors (GABAAR), members of the superfamily of pentameric ligand-gated ion channels (pLGICs) that contain anion-selective channels. Propofol also inhibits pLGICs containing cation-selective channels, including nicotinic acetylcholine receptors and GLIC, a prokaryotic proton-gated homologue from Gloeobacter violaceus . In the structure of GLIC cocrystallized with propofol at pH 4 (presumed open/desensitized states), propofol was localized to an intrasubunit pocket at the extracellular end of the transmembrane domain within the bundle of transmembrane α-helices (Nury, H, et al. (2011) Nature 469, 428-431). To identify propofol binding sites in GLIC in solution, we used a recently developed photoreactive propofol analogue (2-isopropyl-5-[3-(trifluoromethyl)-3H-diazirin-3-yl]phenol or AziPm) that acts as an anesthetic in vivo and potentiates GABAAR in vitro. For GLIC expressed in Xenopus oocytes, propofol and AziPm inhibited current responses at pH 5.5 (EC20) with IC50 values of 20 and 50 μM, respectively. When [(3)H]AziPm (7 μM) was used to photolabel detergent-solubilized, affinity-purified GLIC at pH 4.4, protein microsequencing identified propofol-inhibitable photolabeling of three residues in the GLIC transmembrane domain: Met-205, Tyr-254, and Asn-307 in the M1, M3, and M4 transmembrane helices, respectively. Thus, for GLIC in solution, propofol and AziPm bind competitively to a site in proximity to these residues, which, in the GLIC crystal structure, are in contact with the propofol bound in the intrasubunit pocket.
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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.