Molecular exploration of the α(1A)-adrenoceptor orthosteric site: binding site definition for epinephrine, HEAT and prazosin.
FEBS Lett
; 588(24): 4613-9, 2014 Dec 20.
Article
em En
| MEDLINE
| ID: mdl-25447534
ABSTRACT
Despite the physiological and pharmacological importance of the α1A-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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ligação Competitiva
/
Prazosina
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Epinefrina
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Receptores Adrenérgicos alfa 1
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Tetralonas
Limite:
Animals
Idioma:
En
Revista:
FEBS Lett
Ano de publicação:
2014
Tipo de documento:
Article