ArticleThe Journal of biological chemistry2017
Barbiturates Bind in the GLIC Ion Channel Pore and Cause Inhibition by Stabilizing a Closed State.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- General anesthetic modulation of a pentameric ligand-gated ion channel explored with simulations.Biophysical journal · 2026Article
- Identification of a binding site for bupropion inbioRxiv : the preprint server for biology · 2023Article
- Probing solution structure of the pentameric ligand-gated ion channel GLIC by small-angle neutron scattering.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Dynamic closed states of a ligand-gated ion channel captured by cryo-EM and simulations.Life science alliance · 2021Article
- Structural evidence for the binding of monocarboxylates and dicarboxylates at pharmacologically relevant extracellular sites of a pentameric ligand-gated ion channel.Acta crystallographica. Section D, Structural biology · 2020Article
- Towards a Comprehensive Understanding of Anesthetic Mechanisms of Action: A Decade of Discovery.Trends in pharmacological sciences · 2019Review
- 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
- 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
- Combining Mutations and Electrophysiology to Map Anesthetic Sites on Ligand-Gated Ion Channels.Methods in enzymology · 2018Review
- X-Ray Crystallographic Studies for Revealing Binding Sites of General Anesthetics in Pentameric Ligand-Gated Ion Channels.Methods in enzymology · 2018Article
- Article
- Enantiomeric barbiturates bind distinct inter- and intrasubunit binding sites in a nicotinic acetylcholine receptor (nAChR).The Journal of biological chemistry · 2017Article
- 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
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Barbiturates induce anesthesia by modulating the activity of anionic and cationic pentameric ligand-gated ion channels (pLGICs). Despite more than a century of use in clinical practice, the prototypic binding site for this class of drugs within pLGICs is yet to be described. In this study, we present the first X-ray structures of barbiturates bound to GLIC, a cationic prokaryotic pLGIC with excellent structural homology to other relevant channels sensitive to general anesthetics and, as shown here, to barbiturates, at clinically relevant concentrations. Several derivatives of barbiturates containing anomalous scatterers were synthesized, and these derivatives helped us unambiguously identify a unique barbiturate binding site within the central ion channel pore in a closed conformation. In addition, docking calculations around the observed binding site for all three states of the receptor, including a model of the desensitized state, showed that barbiturates preferentially stabilize the closed state. The identification of this pore binding site sheds light on the mechanism of barbiturate inhibition of cationic pLGICs and allows the rationalization of several structural and functional features previously observed for barbiturates.
Indexed as
Identifiers
What OpenQuestion holds
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.