Amino acids of the α 1B‐adrenergic receptor involved in agonist binding: differences in docking catecholamines to receptor subtypes

FEBS Letters

Cavalli, Antonella¹  Cotecchia, Susanna¹  Taddei, Carlo³  Fanelli, Francesca²  De Benedetti, Pier G.² 

[1] Institut de Pharmacologie et Toxicologie, Université de Lausanne, 1005 Lausanne, Switzerland;Dipartimento di Chimica, Università di Modena, 41100 Modena, Italy;Recordati, Milan, Italy

关键词: G protein-coupled receptor;    Adrenergic receptor;    Catecholamine;    Molecular dynamics;   

DOI  :  10.1016/S0014-5793(96)01286-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Site-directed mutagenesis and molecular dynamics analysis of the 3-D model of the α _1B -adrenergic receptor (AR) were combined to identify the molecular determinants of the receptor involved in catecholamine binding. Our results indicate that the three conserved serines in the fifth transmembrane domain (TMD) of the α _1B-AR play a distinct role in catecholamine binding versus receptor activation. In addition to the amino acids D125 in TMDIII and S207 in TMDV directly involved in ligand binding, our findings identify a large number of polar residues playing an important role in the activation process of the α _1B-AR thus providing new insights into the structure/function relationship of G protein-coupled receptors.

【 授权许可】

Unknown