Ligand binding adrenergic receptors

Wang CD, Buck MA, Fraser CM. Site-directed mutagenesis of a2A-adrenergic receptors—identification of amino-acids involved in ligand-binding and receptor activation by agonists. Mol Pharmacol 1991 40 168-179. 

Thus three lines of evidence define the rapidly dissociating receptor as the LR complex. Conditions known to uncouple R from G--first, guanine nucleotide and second, pertussis toxin—produce LR third, reconstitution of G protein restores receptor affinity, sensitivity to guanine nucleotide, and effector activation. In this sense, the ligand and binding behavior of this system is analogous to that of the beta-adrenergic receptor, where the LR and LRG complexes have already been studied with purified proteins and reconstituted membrane preparations (2,i0). 

M, Ligett SB. A polymorphism of the human /f adrenergic receptor within the fourth transmembrane domain alters ligand binding and functional properties of the receptor. J Biol Chem 1993 268 23116-23121. 

Strader C, Sigal I, Register R, Cande-lore M, Rands E, Dixon R. Identification of residues required for ligand binding to the beta-adrenergic receptor. Proc Natl Acad Sci USA 1987 84 4384-4388. 

The best statistical parameters were obtained by correlating the in vivo selectivity with the Vdif descriptor defined with respect to the oqa-AR supermolecule. It is worth noting that the oqa is the adrenergic receptor subtype of functional relevance for the urethra tissue (dog model) [8]. Thus, ligands showing high potency and selectivity for the lower urinary tract are those, which better fit the volume of the supermolecule that represents the binding site of the ala-AR subtype. 

The adrenergic receptors (or adrenoceptors) are a class of G-protein coupled receptors, which are the targets of catecholamines. Adrenergic receptors specifically bind their endogenous ligands, the catecholamines, epinephrine, and norepinephrine (also called adrenaline and noradrenaline), and are activated by these. 

Fig. 5.6. Topology of the P-adrenergic receptor of hamster. The primary structure is shown of the P-receptor for adrenaline from hamster, with the assumed topology of the seven transmembrane helices. The extracellular domain is shown at the top of the picture. The interface of the ceU membrane is indicated by the dashed line. The filled squares show glycosylation sites. Amino adds not required for ligand binding, according to mutagenesis studies, are shown as open squares. Reprinted with permission of the American Journal of Respiratory Cell and Molecular Biology (1989), 1, No.2, p.82.

Touhara, K. Binding of multiple ligands to pleckstrin homology domain regulates membrane translocation and enzyme activity of -adrenergic receptor kinase. FEBS Lett., 417, 243-248 (1997)... 

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