Search for structural basis of interactions of biogenic amines with human taar1 and taar6 receptors

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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.

в: International Journal of Molecular Sciences, Том 23, № 1, 209, 01.01.2022.

Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование

BibTeX

@article{fb370ca7d1734cb5be6fa480ca319c3c,

title = "Search for structural basis of interactions of biogenic amines with human taar1 and taar6 receptors",

abstract = "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.",

keywords = "Cadaverine, Gamma-aminobutyric acid (GABA), Putrescine, TAAR1, TAAR6, Trace amine receptors, Trace amines, Tyramine, β-phenylethylamine, Phenethylamines/metabolism, Amino Acid Sequence, Humans, Binding Sites/physiology, Cadaverine/metabolism, Cell Cycle Proteins/metabolism, Tyramine/metabolism, gamma-Aminobutyric Acid/metabolism, Fishes/metabolism, Animals, Putrescine/metabolism, Biogenic Amines/metabolism, Receptors, G-Protein-Coupled/metabolism, Ligands, Mice, ALLOSTERIC MODULATORS, TRACE AMINES, CHEMOSENSORY RECEPTORS, trace amine receptors, trace amines, FAMILY, URINE, gamma-aminobutyric acid (GABA), putrescine, cadaverine, CADAVERINE, beta-phenylethylamine, SERUM, tyramine, GPCRS, OLFACTORY RECEPTOR",

author = "Glyakina, {Anna V.} and Pavlov, {Constantine D.} and Sopova, {Julia V.} and Gainetdinov, {Raul R.} and Leonova, {Elena I.} and Galzitskaya, {Oxana V.}",

note = "Glyakina, A.V.; Pavlov, C.D.; Sopova, J.V.; Gainetdinov, R.R.; Leonova, E.I.; Galzitskaya, O.V. Search for Structural Basis of Interactions of Biogenic Amines with Human TAAR1 and TAAR6 Receptors. Int. J. Mol. Sci. 2022, 23, 209. https://doi.org/10.3390/ijms23010209",

year = "2022",

month = jan,

day = "1",

doi = "10.3390/ijms23010209",

language = "English",

volume = "23",

journal = "International Journal of Molecular Sciences",

issn = "1422-0067",

publisher = "MDPI AG",

number = "1",

}

RIS

TY - JOUR

T1 - Search for structural basis of interactions of biogenic amines with human taar1 and taar6 receptors

AU - Glyakina, Anna V.

AU - Pavlov, Constantine D.

AU - Sopova, Julia V.

AU - Gainetdinov, Raul R.

AU - Leonova, Elena I.

AU - Galzitskaya, Oxana V.

N1 - Glyakina, A.V.; Pavlov, C.D.; Sopova, J.V.; Gainetdinov, R.R.; Leonova, E.I.; Galzitskaya, O.V. Search for Structural Basis of Interactions of Biogenic Amines with Human TAAR1 and TAAR6 Receptors. Int. J. Mol. Sci. 2022, 23, 209. https://doi.org/10.3390/ijms23010209

PY - 2022/1/1

Y1 - 2022/1/1

N2 - 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.

AB - 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.

KW - Cadaverine

KW - Gamma-aminobutyric acid (GABA)

KW - Putrescine

KW - TAAR1

KW - TAAR6

KW - Trace amine receptors

KW - Trace amines

KW - Tyramine

KW - β-phenylethylamine

KW - Phenethylamines/metabolism

KW - Amino Acid Sequence

KW - Humans

KW - Binding Sites/physiology

KW - Cadaverine/metabolism

KW - Cell Cycle Proteins/metabolism

KW - Tyramine/metabolism

KW - gamma-Aminobutyric Acid/metabolism

KW - Fishes/metabolism

KW - Animals

KW - Putrescine/metabolism

KW - Biogenic Amines/metabolism

KW - Receptors, G-Protein-Coupled/metabolism

KW - Ligands

KW - Mice

KW - ALLOSTERIC MODULATORS

KW - TRACE AMINES

KW - CHEMOSENSORY RECEPTORS

KW - trace amine receptors

KW - trace amines

KW - FAMILY

KW - URINE

KW - gamma-aminobutyric acid (GABA)

KW - putrescine

KW - cadaverine

KW - CADAVERINE

KW - beta-phenylethylamine

KW - SERUM

KW - tyramine

KW - GPCRS

KW - OLFACTORY RECEPTOR

UR - http://www.scopus.com/inward/record.url?scp=85121601033&partnerID=8YFLogxK

U2 - 10.3390/ijms23010209

DO - 10.3390/ijms23010209

M3 - Article

C2 - 35008636

AN - SCOPUS:85121601033

VL - 23

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 1

M1 - 209

ER -

ID: 93026896