ArticleBiochemistry2012
Mapping general anesthetic binding site(s) in human α1β3 γ-aminobutyric acid type A receptors with [³H]TDBzl-etomidate, a photoreactive etomidate analogue.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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68 citing papers in PubMed, 104 citations in OpenAlex.
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- The difference in mean arterial pressure induced by remimazolam compared to etomidate in the presence of fentanyl at tracheal intubation: A randomized controlled trial.Frontiers in pharmacology · 2023Article
- Modulation of the mammalian GABABritish journal of pharmacology · 2022Article
- GABAJournal, genetic engineering & biotechnology · 2021Review
- Direct Structural Insights into GABATrends in biochemical sciences · 2021Review
- Druggable Lipid Binding Sites in Pentameric Ligand-Gated Ion Channels and Transient Receptor Potential Channels.Frontiers in physiology · 2021Review
- Article
- Photoaffinity labeling identifies an intersubunit steroid-binding site in heteromeric GABA type A (GABAThe Journal of biological chemistry · 2020Article
- A potent photoreactive general anesthetic with novel binding site selectivity for GABAEuropean journal of medicinal chemistry · 2020Article
- GABAInternational journal of molecular sciences · 2020Article
- Identifying Drugs that Bind Selectively to Intersubunit General Anesthetic Sites in theMolecular pharmacology · 2019Article
- Inhibitable photolabeling by neurosteroid diazirine analog in the β3-Subunit of human hetereopentameric type A GABA receptors.European journal of medicinal chemistry · 2019Article
- Etomidate and Etomidate Analog Binding and Positive Modulation of γ-Aminobutyric Acid Type A Receptors: Evidence for a State-dependent Cutoff Effect.Anesthesiology · 2018Article
- Structural basis of neurosteroid anesthetic action on GABANature communications · 2018Article
- Identification of binding sites contributing to volatile anesthetic effects on GABA type A receptors.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Comparison of αβδ and αβγ GABAPharmacological research · 2018Review
- Permeating disciplines: Overcoming barriers between molecular simulations and classical structure-function approaches in biological ion transport.Biochimica et biophysica acta. Biomembranes · 2018Review
8 more citing papers are in PubMed but not listed here.
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6 authors at 2 institutions in 1 country.
Funding
Abstract
The γ-aminobutyric acid type A receptor (GABA(A)R) is a target for general anesthetics of diverse chemical structures, which act as positive allosteric modulators at clinical doses. Previously, in a heterogeneous mixture of GABA(A)Rs purified from bovine brain, [³H]azietomidate photolabeling of αMet-236 and βMet-286 in the αM1 and βM3 transmembrane helices identified an etomidate binding site in the GABA(A)R transmembrane domain at the interface between the β and α subunits [Li, G. D., et.al. (2006) J. Neurosci. 26, 11599-11605]. To further define GABA(A)R etomidate binding sites, we now use [³H]TDBzl-etomidate, an aryl diazirine with broader amino acid side chain reactivity than azietomidate, to photolabel purified human FLAG-α1β3 GABA(A)Rs and more extensively identify photolabeled GABA(A)R amino acids. [³H]TDBzl-etomidate photolabeled in an etomidate-inhibitable manner β3Val-290, in the β3M3 transmembrane helix, as well as α1Met-236 in α1M1, a residue photolabeled by [³H]azietomidate, while no photolabeling of amino acids in the αM2 and βM2 helices that also border the etomidate binding site was detected. The location of these photolabeled amino acids in GABA(A)R homology models derived from the recently determined structures of prokaryote (GLIC) or invertebrate (GluCl) homologues and the results of computational docking studies predict the orientation of [³H]TDBzl-etomidate bound in that site and the other amino acids contributing to this GABA(A)R intersubunit etomidate binding site. Etomidate-inhibitable photolabeling of β3Met-227 in βM1 by [³H]TDBzl-etomidate and [³H]azietomidate also provides evidence of a homologous etomidate binding site at the β3-β3 subunit interface in the α1β3 GABA(A)R.
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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.