ArticlePloS one2013
A unified model of the GABA(A) receptor comprising agonist and benzodiazepine binding sites.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed.
- Targeting Anti-Inflammatory Pathways to Treat Diabetes-Induced Neuropathy by 6-Hydroxyflavanone.Nutrients · 2023Article
- Allosteric modulation of α1β3γ2 GABABiophysical journal · 2023Article
- Glutamate and GABASignal transduction and targeted therapy · 2022Article
- The Case for Clinical Trials with Novel GABAergic Drugs in Diabetes Mellitus and Obesity.Life (Basel, Switzerland) · 2022Article
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- Comprehensive Genome-Wide Identification and Transcript Profiling of GABA Pathway Gene Family in Apple (Genes · 2021Article
- Photopharmacology of Ion Channels through the Light of the Computational Microscope.International journal of molecular sciences · 2021Review
- Synthesis and Pharmacological Evaluation of Novel 2,3,4,5-tetrahydro[1,3]diazepino[1,2-Molecules (Basel, Switzerland) · 2021Article
- GABAJournal, genetic engineering & biotechnology · 2021Review
- 5-International journal of molecular sciences · 2021Article
- Rational approaches for the design of various GABA modulators and their clinical progression.Molecular diversity · 2021Review
- Involvement of GABABioMed research international · 2021Article
- Optopharmacology reveals a differential contribution of native GABANeuropharmacology · 2020Article
- Pathophysiology of and therapeutic options for a GABRA1 variant linked to epileptic encephalopathy.Molecular brain · 2019Article
- Article
- A photoswitchable GABA receptor channel blocker.British journal of pharmacology · 2019Article
- Diverse role of γ-aminobutyric acid in dynamic plant cell responses.Plant cell reports · 2019Review
- Concatenated γ-aminobutyric acid type A receptors revisited: Finding order in chaos.The Journal of general physiology · 2019Article
- Amino acid substitutions in the human homomeric βThe Journal of biological chemistry · 2019Article
- A mutational and molecular dynamics study of the cys-loop GABA receptor Hco-UNC-49 from Haemonchus contortus: Agonist recognition in the nematode GABA receptor family.International journal for parasitology. Drugs and drug resistance · 2018Article
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5 authors.
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Abstract
We present a full-length α(1)β(2)γ(2) GABA receptor model optimized for agonists and benzodiazepine (BZD) allosteric modulators. We propose binding hypotheses for the agonists GABA, muscimol and THIP and for the allosteric modulator diazepam (DZP). The receptor model is primarily based on the glutamate-gated chloride channel (GluCl) from C. elegans and includes additional structural information from the prokaryotic ligand-gated ion channel ELIC in a few regions. Available mutational data of the binding sites are well explained by the model and the proposed ligand binding poses. We suggest a GABA binding mode similar to the binding mode of glutamate in the GluCl X-ray structure. Key interactions are predicted with residues α(1)R66, β(2)T202, α(1)T129, β(2)E155, β(2)Y205 and the backbone of β(2)S156. Muscimol is predicted to bind similarly, however, with minor differences rationalized with quantum mechanical energy calculations. Muscimol key interactions are predicted to be α(1)R66, β(2)T202, α(1)T129, β(2)E155, β(2)Y205 and β(2)F200. Furthermore, we argue that a water molecule could mediate further interactions between muscimol and the backbone of β(2)S156 and β(2)Y157. DZP is predicted to bind with interactions comparable to those of the agonists in the orthosteric site. The carbonyl group of DZP is predicted to interact with two threonines α(1)T206 and γ(2)T142, similar to the acidic moiety of GABA. The chlorine atom of DZP is placed near the important α(1)H101 and the N-methyl group near α(1)Y159, α(1)T206, and α(1)Y209. We present a binding mode of DZP in which the pending phenyl moiety of DZP is buried in the binding pocket and thus shielded from solvent exposure. Our full length GABA(A) receptor is made available as Model S1.
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