7ARO
Crystal structure of the non-ribose partial agonist LUF5833 bound to the adenosine A2A receptor
Summary for 7ARO
| Entry DOI | 10.2210/pdb7aro/pdb |
| Descriptor | Adenosine receptor A2a,Soluble cytochrome b562,Adenosine receptor A2a, 2-azanyl-6-(1~{H}-imidazol-2-ylmethylsulfanyl)-4-phenyl-pyridine-3,5-dicarbonitrile, OLEIC ACID, ... (6 entities in total) |
| Functional Keywords | g protein-coupled receptor, gpcr, receptor, partial agonist, membrane protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 49868.62 |
| Authors | Verdon, G.,Amelia, T.,van Veldhoven, J.,Falsini, M.,Liu, R.,Heitman, L.,van Westen, G.,Segala, E.,Cheng, R.,Cooke, R.,van der Es, D.,Ijzerman, A. (deposition date: 2020-10-25, release date: 2021-04-07, Last modification date: 2024-01-31) |
| Primary citation | Amelia, T.,van Veldhoven, J.P.D.,Falsini, M.,Liu, R.,Heitman, L.H.,van Westen, G.J.P.,Segala, E.,Verdon, G.,Cheng, R.K.Y.,Cooke, R.M.,van der Es, D.,IJzerman, A.P. Crystal Structure and Subsequent Ligand Design of a Nonriboside Partial Agonist Bound to the Adenosine A 2A Receptor. J.Med.Chem., 64:3827-3842, 2021 Cited by PubMed Abstract: In this study, we determined the crystal structure of an engineered human adenosine A 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. PubMed: 33764785DOI: 10.1021/acs.jmedchem.0c01856 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.119 Å) |
Structure validation
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