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Article Dans Une Revue FEBS Letters Année : 2014

Molecular exploration of the $\alpha_{1A}$-adrenoceptor orthosteric site: Binding site definition for epinephrine, HEAT and prazosin

Résumé

Despite the physiological and pharmacological importance of the $\alpha_{1A}$-adrenoreceptor, the mode of interactions of classical agonists and radioactive ligands with this receptor is not yet clearly defined. Here, we used mutagenesis studies and binding experiments to evaluate the importance of 11 receptor sites for the binding of $^{125}$I-HEAT, $^3$H-prazosin and epinephrine. Only one residue (F312) commonly interacts with the three molecules, and, surprisingly, D106 interacts only with epinephrine in a moderate way. Our docking model shows that prazosin and HEAT are almost superimposed into the orthosteric pocket with their tetralone and quinazoline rings close to the phenyl ring of the agonist.

Dates et versions

hal-03633247 , version 1 (06-04-2022)

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Arhamatoulaye Maïga, Mélanie Dupont, Guillaume Blanchet, Elodie Marcon, Bernard Gilquin, et al.. Molecular exploration of the $\alpha_{1A}$-adrenoceptor orthosteric site: Binding site definition for epinephrine, HEAT and prazosin. FEBS Letters, 2014, 588 (24), pp.4613-4619. ⟨10.1016/j.febslet.2014.10.033⟩. ⟨hal-03633247⟩
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