scholarly journals Search for Structural Basis of Interactions of Biogenic Amines with Human TAAR1 and TAAR6 Receptors

2021 ◽  
Vol 23 (1) ◽  
pp. 209
Author(s):  
Anna V. Glyakina ◽  
Constantine D. Pavlov ◽  
Julia V. Sopova ◽  
Raul R. Gainetdinov ◽  
Elena I. Leonova ◽  
...  
Keyword(s):  
Biogenic Amines ◽  
Binding Sites ◽  
Aminobutyric Acid ◽  
Structural Basis ◽  
Gamma Aminobutyric Acid ◽  
Class A ◽  
Trace Amine ◽  
First Time ◽  
Identification And Characterization

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.

Gamma-aminobutyric acid-modulated benzodiazepine binding sites in bacteria

Life Sciences ◽  
1991 ◽  
Vol 49 (15) ◽  
pp. 1079-1086 ◽  
Author(s):  
Sarah C.R. Lummis ◽  
Gina Nicoletti ◽  
Graham A.R. Johnston ◽  
George Holan
Keyword(s):  
Binding Sites ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Benzodiazepine Binding ◽  
Benzodiazepine Binding Sites

scholarly journals Identification and Characterization of α-Glucosidase Inhibition Flavonol Glycosides from Jack Bean (Canavalia ensiformis (L.) DC

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2481
Author(s):  
Anita M. Sutedja ◽  
Emiko Yanase ◽  
Irmanida Batubara ◽  
Dedi Fardiaz ◽  
Hanifah N. Lioe
Keyword(s):  
2D Nmr ◽  
The Other ◽  
Inhibition Activity ◽  
Jack Bean ◽  
Canavalia Ensiformis ◽  
Kaempferol Glycosides ◽  
Uv Visible ◽  
First Time ◽  
Identification And Characterization

Although the intake of jack bean (Canavalia ensiformis (L.) DC.), an underutilized tropical legume, can potentially decrease the risk of several chronic diseases, not much effort has been directed at profiling the polyphenolics contained therein. Hence, this work aimed to identify and quantify the dominant jack bean polyphenolics, which are believed to have antioxidant and other bioactivities. Four major compounds were detected and identified as kaempferol glycosides with three or four glycoside units. Their structures were established based on UV-visible, 1D, 2D NMR, and HR-ESI-MS analyses. Specifically, kaempferol 3-O-α-l-rhamnopyranosyl (1→6)- β-d-glucopyranosyl (1→2)-β-d-galactopyranosyl-7-O-[3-O-o-anisoyl]-α-l-rhamnopyranoside was detected for the first time, while the other three compounds have already been described in plants other than jack bean. This new compound was found to have a higher α-glucosidase inhibition activity compared to acarbose.

scholarly journals Identification and characterization of carbapenem binding sites within the RND-transporter AcrB

2019 ◽  
Vol 1861 (1) ◽  
pp. 62-74 ◽  
Author(s):  
Alessio Atzori ◽  
Viveka N. Malviya ◽  
Giuliano Malloci ◽  
Jürg Dreier ◽  
Klaas M. Pos ◽  
...  
Keyword(s):  
Binding Sites ◽  
Rnd Transporter ◽  
Identification And Characterization

Identification of gamma-aminobutyric acid and its binding sites in

Life Sciences ◽  
1988 ◽  
Vol 43 (21) ◽  
pp. 1701-1706 ◽  
Author(s):  
James M. Schaeffer ◽  
Alan R. Bergstrom
Keyword(s):  
Binding Sites ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid

Identification and characterization of a corticotrophin-releasing hormone receptor in human placenta

1995 ◽  
Vol 133 (5) ◽  
pp. 591-597 ◽  
Author(s):  
Vicki L Clifton ◽  
Phillip C Owens ◽  
Phillip J Robinson ◽  
Roger Smith
Keyword(s):  
Human Placenta ◽  
Binding Sites ◽  
Hormone Receptor ◽  
Human Myometrium ◽  
Scatchard Analysis ◽  
Releasing Hormone ◽  
Rat Pituitary ◽  
Identification And Characterization ◽  
Crh Receptors

Clifton VL, Owens PC, Robinson PJ, Smith R. Identification and characterization of a corticotrophinreleasing hormone receptor in human placenta. Eur J Endocrinol 1995;133:591–7. ISSN 0804–4643 Corticotrophin-releasing hormone (CRH) causes vasodilatation in the human fetal–placental circulation and has paracrine actions in placental tissue, suggesting that CRH receptors may be present in the human placenta. We have now identified and characterized placental CRH binding sites and compared them to those described previously in human myometrium and rat pituitary. Radiolabelled ovine CRH binding to placental membranes was pH-, time-, temperature- and divalent cation-dependent and was reversible in the presence of 1 μmol/l unlabelled ovine CRH. Scatchard analysis of placentae delivered vaginally or by elective caesarean section revealed dissociation constants (Kd) of 214.5 ± 84 pmol/l (N = 8) and 45.4 ± 23.9 pmol/l (N = 9), respectively. The Kd for caesarean placental binding sites was similar to that of human myometrium (59.6 pmol/l, N = 3) and rat pituitary (82.5 pmol/l, N = 3) receptors. However, in vaginally delivered placentae the CRH binding sites had a much lower affinity (p < 0.05). The receptor densities (Bmax) of vaginally delivered and caesarean-delivered placentae were 28.6 ± 9.6 and 6.1 ± 2.8 fmol/mg, respectively (p < 0.05). Chemical cross-linking studies using disuccinimidyl suberate indicated that the molecular weight of the CRH receptor in the placenta and rat pituitary is 75 kD. We conclude that there is a high-affinity population of CRH binding sites in the human placenta that are physicochemically similar to pituitary and myometrial CRH receptors. The CRH receptor properties in the placenta change in response to labour, when CRH levels in maternal blood are highest, suggesting that placental CRH may regulate its receptor. R Smith, Endocrinology Unit, John Hunter Hospital, Locked Bag 1, Hunter Regional Mail Centre, Newcastle, NSW 2310, Australia

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