The GABAB Receptor - Structure, Ligand Binding and Drug Development
| Autor: | Mari Gabrielsen, Linn Samira Mari Evenseth, Ingebrigt Sylte |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Protein Conformation alpha-Helical Agonist Baclofen GABAB receptors orthosteric binding site medicine.drug_class Pharmaceutical Science Review GABAB receptor Neurotransmission Ligands allosteric binding site Analytical Chemistry lcsh:QD241-441 03 medical and health sciences chemistry.chemical_compound structural mechanisms 0302 clinical medicine lcsh:Organic chemistry Drug Discovery medicine Humans Physical and Theoretical Chemistry Receptor 030304 developmental biology G protein-coupled receptor 0303 health sciences Binding Sites GABAA receptor VDP::Medical disciplines: 700::Basic medical dental and veterinary science disciplines: 710::Pharmacology: 728 Organic Chemistry drug development Transmembrane domain Receptors GABA-B chemistry Chemistry (miscellaneous) Molecular Medicine VDP::Medisinske Fag: 700::Basale medisinske odontologiske og veterinærmedisinske fag: 710::Farmakologi: 728 GABA-B Receptor Antagonists Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Molecules Molecules, Vol 25, Iss 3093, p 3093 (2020) |
| Popis: | The γ-aminobutyric acid (GABA) type B receptor (GABAB-R) belongs to class C of the G-protein coupled receptors (GPCRs). Together with the GABAA receptor, the receptor mediates the neurotransmission of GABA, the main inhibitory neurotransmitter in the central nervous system (CNS). In recent decades, the receptor has been extensively studied with the intention being to understand pathophysiological roles, structural mechanisms and develop drugs. The dysfunction of the receptor is linked to a broad variety of disorders, including anxiety, depression, alcohol addiction, memory and cancer. Despite extensive efforts, few compounds are known to target the receptor, and only the agonist baclofen is approved for clinical use. The receptor is a mandatory heterodimer of the GABAB1 and GABAB2 subunits, and each subunit is composed of an extracellular Venus Flytrap domain (VFT) and a transmembrane domain of seven α-helices (7TM domain). In this review, we briefly present the existing knowledge about the receptor structure, activation and compounds targeting the receptor, emphasizing the role of the receptor in previous and future drug design and discovery efforts. |
| Databáze: | OpenAIRE |
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