Molecular modeling of adenosine receptors. The ligand binding site on the rat adenosine A2A receptor.

ABSTRACT: The amino acid sequence of the rat adenosine A2A receptor and the atomic coordinates of bacteriorhodopsin were combined to generate a three-dimensional model for the adenosine A2A receptor. This model consists of seven amphipathic alpha-helices, forming a pore that is rather hydrophilic compared to the hydrophobic outside of the protein. Subsequently, a highly potent and selective ligand for this receptor, 2-(cyclohexylmethylidinehydrazino)adenosine (SHA 174), was docked into this cavity. A binding site is proposed that takes into account the conformational characteristics of the ligand. Moreover, it involves two histidine residues that were shown to be important for ligand coordination from chemical modification studies. Subsequently, the deduced binding site was used to model other poten

SUBMITTER: IJzerman AP 

PROVIDER: S-EPMC6939755 | biostudies-literature | 1994 Jun

REPOSITORIES: biostudies-literature