Figure 1. Chemical structures of ligands and overview of the A_2AAR orthosteric binding site.

Structures of the antagonist ZM241385 (A) and the agonist NECA (B) are depicted together with compounds used as radioligands in the experimental site-directed mutagenesis considered in this work (see Tables 1, 2). (C) ZM241385 (green sticks) and NECA (magenta sticks) overlaid in the orthosteric binding site [9], [10]. Receptor residues examined by alanine scanning are shown as spheres for antagonist binding (green), agonist binding (magenta) or both agonist and antagonist binding (yellow).