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Search for Structural Basis of Interactions of Biogenic Amines with Human TAAR1 and TAAR6 Receptors
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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745718/ https://www.ncbi.nlm.nih.gov/pubmed/35008636 http://dx.doi.org/10.3390/ijms23010209 |
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author | Glyakina, Anna V. Pavlov, Constantine D. Sopova, Julia V. Gainetdinov, Raul R. Leonova, Elena I. Galzitskaya, Oxana V. |
author_facet | Glyakina, Anna V. Pavlov, Constantine D. Sopova, Julia V. Gainetdinov, Raul R. Leonova, Elena I. Galzitskaya, Oxana V. |
author_sort | Glyakina, Anna V. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8745718 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87457182022-01-11 Search for Structural Basis of Interactions of Biogenic Amines with Human TAAR1 and TAAR6 Receptors Glyakina, Anna V. Pavlov, Constantine D. Sopova, Julia V. Gainetdinov, Raul R. Leonova, Elena I. Galzitskaya, Oxana V. Int J Mol Sci Article 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. MDPI 2021-12-25 /pmc/articles/PMC8745718/ /pubmed/35008636 http://dx.doi.org/10.3390/ijms23010209 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Glyakina, Anna V. Pavlov, Constantine D. Sopova, Julia V. Gainetdinov, Raul R. Leonova, Elena I. Galzitskaya, Oxana V. Search for Structural Basis of Interactions of Biogenic Amines with Human TAAR1 and TAAR6 Receptors |
title | Search for Structural Basis of Interactions of Biogenic Amines with Human TAAR1 and TAAR6 Receptors |
title_full | Search for Structural Basis of Interactions of Biogenic Amines with Human TAAR1 and TAAR6 Receptors |
title_fullStr | Search for Structural Basis of Interactions of Biogenic Amines with Human TAAR1 and TAAR6 Receptors |
title_full_unstemmed | Search for Structural Basis of Interactions of Biogenic Amines with Human TAAR1 and TAAR6 Receptors |
title_short | Search for Structural Basis of Interactions of Biogenic Amines with Human TAAR1 and TAAR6 Receptors |
title_sort | search for structural basis of interactions of biogenic amines with human taar1 and taar6 receptors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745718/ https://www.ncbi.nlm.nih.gov/pubmed/35008636 http://dx.doi.org/10.3390/ijms23010209 |
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