Search for Structural Basis of Interactions of Biogenic Amines with Human TAAR1 and TAAR6 Receptors
| العنوان: | Search for Structural Basis of Interactions of Biogenic Amines with Human TAAR1 and TAAR6 Receptors |
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| المؤلفون: | Anna V. Glyakina, Constantine D. Pavlov, Julia V. Sopova, Raul R. Gainetdinov, Elena I. Leonova, Oxana V. Galzitskaya |
| المصدر: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 23, Iss 209, p 209 (2022) International Journal of Molecular Sciences; Volume 23; Issue 1; Pages: 209 |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | β-phenylethylamine, tyramine, gamma-aminobutyric acid (GABA), cadaverine, putrescine, trace amines, trace amine receptors, TAAR6, TAAR1, Biogenic Amines, QH301-705.5, Tyramine, Cell Cycle Proteins, Ligands, Catalysis, Article, Receptors, G-Protein-Coupled, Inorganic Chemistry, Mice, Phenethylamines, Putrescine, Animals, Humans, Amino Acid Sequence, Physical and Theoretical Chemistry, Biology (General), Molecular Biology, QD1-999, Spectroscopy, gamma-Aminobutyric Acid, Binding Sites, Organic Chemistry, Fishes, General Medicine, Computer Science Applications, Chemistry |
| الوصف: | The identification and characterization of ligand-receptor binding sites are important for drug development. Trace amine-associated receptors (TAARs, members of the class A GPCR family) can interact with different biogenic amines and their metabolites, but the structural basis for their recognition by the TAARs is not well understood. In this work, we have revealed for the first time a group of conserved motifs (fingerprints) characterizing TAARs and studied the docking of aromatic (β-phenylethylamine, tyramine) and aliphatic (putrescine and cadaverine) ligands, including gamma-aminobutyric acid, with human TAAR1 and TAAR6 receptors. We have identified orthosteric binding sites for TAAR1 (Asp68, Asp102, Asp284) and TAAR6 (Asp78, Asp112, Asp202). By analyzing the binding results of 7500 structures, we determined that putrescine and cadaverine bind to TAAR1 at one site, Asp68 + Asp102, and to TAAR6 at two sites, Asp78 + Asp112 and Asp112 + Asp202. Tyramine binds to TAAR6 at the same two sites as putrescine and cadaverine and does not bind to TAAR1 at the selected Asp residues. β-Phenylethylamine and gamma-aminobutyric acid do not bind to the TAAR1 and TAAR6 receptors at the selected Asp residues. The search for ligands targeting allosteric and orthosteric sites of TAARs has excellent pharmaceutical potential. |
| وصف الملف: | application/pdf |
| تدمد: | 1422-0067 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::091b4e7f4894f67236b9a48f30fb9484 https://pubmed.ncbi.nlm.nih.gov/35008636 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....091b4e7f4894f67236b9a48f30fb9484 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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