9EHS
Structure of a human adenosine A3 receptor complex bound to the covalent antagonist LUF7602
This is a non-PDB format compatible entry.
Summary for 9EHS
| Entry DOI | 10.2210/pdb9ehs/pdb |
| EMDB information | 48065 |
| Descriptor | BAG2 Anti-BRIL Fab Heavy Chain, elbow nanobody, BAG2 Anti-BRIL Fab Light Chain, ... (5 entities in total) |
| Functional Keywords | g protein-coupled receptor, adenosine binding, seven transmembrane protein, membrane protein, signaling protein |
| Biological source | synthetic construct More |
| Total number of polymer chains | 4 |
| Total formula weight | 116745.63 |
| Authors | Zhang, L.,Mobbs, J.I.,Glukhova, A.,Thal, D.M. (deposition date: 2024-11-24, release date: 2025-08-20, Last modification date: 2025-09-03) |
| Primary citation | Zhang, L.,Mobbs, J.I.,Bennetts, F.M.,Venugopal, H.,Nguyen, A.T.N.,Christopoulos, A.,van der Es, D.,Heitman, L.H.,May, L.T.,Glukhova, A.,Thal, D.M. Molecular basis of ligand binding and receptor activation at the human A 3 adenosine receptor. Nat Commun, 16:7674-7674, 2025 Cited by PubMed Abstract: Adenosine receptors (ARs: AAR, AAR, AAR, and AAR) are crucial therapeutic targets; however, developing selective, efficacious drugs for them remains a significant challenge. Here, we present high-resolution cryo-electron microscopy (cryo-EM) structures of the human AAR in three distinct functional states: bound to the endogenous agonist adenosine, the clinically relevant agonist Piclidenoson, and the covalent antagonist LUF7602. These structures, complemented by mutagenesis and pharmacological studies, reveal an AAR activation mechanism that involves an extensive hydrogen bond network from the extracellular surface down to the orthosteric binding site. In addition, we identify a cryptic pocket that accommodates the N-iodobenzyl group of Piclidenoson through a ligand-dependent conformational change of M174. Our comprehensive structural and functional characterisation of AAR advances our understanding of adenosine receptor pharmacology and establishes a foundation for developing more selective therapeutics for various disorders, including inflammatory diseases, cancer, and glaucoma. PubMed: 40825947DOI: 10.1038/s41467-025-62872-x PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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