Docking studies of agonists and antagonists suggest an activation pathway of the A3 adenosine receptor.

ABSTRACT: Structural determinants of ligand efficacy in the human A(3) adenosine receptor (AR) were studied using pharmacophore and docking analyses of various categories of A(3) selective ligands: inverse agonist, neutral antagonist (nonnucleoside and nucleoside), and agonist (partial and full). The homology modeling of GPCRs was adapted to provide two templates: the rhodopsin-based resting state for antagonist binding and a putative Meta I state, conformationally altered at a key residue (W6.48), for agonist binding. The preferential binding domains and/or local conformational changes associated with docking of three high affinity A(3)AR ligands were compared: inverse agonist PSB-11 1 ((R)-8-ethyl-4-methyl-2-phenyl-imidazo[2,1-i]purin-5-one); neutral antagonist MRE-3008F20 7 (5-[[(4-methoxyphenyl)

SUBMITTER: Kim SK 

PROVIDER: S-EPMC6262875 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature