Structural highlights
Function[AA2AR_HUMAN] Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. Publication Abstract from PubMedIn this study, we determined the crystal structure of an engineered human adenosine A2A receptor bound to a partial agonist and compared it to structures cocrystallized with either a full agonist or an antagonist/inverse agonist. The interaction between the partial agonist, belonging to a class of dicyanopyridines, and amino acids in the ligand binding pocket inspired us to develop a small library of derivatives and assess their affinity in radioligand binding studies and potency and intrinsic activity in a functional, label-free, intact cell assay. It appeared that some of the derivatives retained the partial agonist profile, whereas other ligands turned into inverse agonists. We rationalized this remarkable behavior with additional computational docking studies. Crystal Structure and Subsequent Ligand Design of a Nonriboside Partial Agonist Bound to the Adenosine A2A Receptor.,Amelia T, van Veldhoven JPD, Falsini M, Liu R, Heitman LH, van Westen GJP, Segala E, Verdon G, Cheng RKY, Cooke RM, van der Es D, IJzerman AP J Med Chem. 2021 Mar 25. doi: 10.1021/acs.jmedchem.0c01856. PMID:33764785[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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