6AQF
Crystal structure of A2AAR-BRIL in complex with the antagonist ZM241385 produced from Pichia pastoris
Summary for 6AQF
| Entry DOI | 10.2210/pdb6aqf/pdb |
| Descriptor | Adenosine receptor A2a,Soluble cytochrome b562,Adenosine receptor A2a, 4-{2-[(7-amino-2-furan-2-yl[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-yl)amino]ethyl}phenol, CHOLESTEROL, ... (7 entities in total) |
| Functional Keywords | a2aar, gpcr, adenosine receptor, human a2aar_bril chimera, lcp, antagonist complex, pichia pastoris, membrane protein |
| Biological source | Homo sapiens (Human) More |
| Cellular location | Cell membrane; Multi-pass membrane protein: P29274 |
| Total number of polymer chains | 1 |
| Total formula weight | 53546.41 |
| Authors | Eddy, M.T.,Lee, M.Y.,Gao, Z.,White, K.,Didenko, T.,Horst, R.,Audet, M.,Stanczak, P.,McClary, K.M.,Han, G.W.,Jacobson, K.A.,Stevens, R.C.,Wuthrich, K. (deposition date: 2017-08-19, release date: 2018-01-10, Last modification date: 2024-10-16) |
| Primary citation | Eddy, M.T.,Lee, M.Y.,Gao, Z.G.,White, K.L.,Didenko, T.,Horst, R.,Audet, M.,Stanczak, P.,McClary, K.M.,Han, G.W.,Jacobson, K.A.,Stevens, R.C.,Wuthrich, K. Allosteric Coupling of Drug Binding and Intracellular Signaling in the A2A Adenosine Receptor. Cell, 172:68-80.e12, 2018 Cited by PubMed Abstract: Signaling across cellular membranes, the 826 human G protein-coupled receptors (GPCRs) govern a wide range of vital physiological processes, making GPCRs prominent drug targets. X-ray crystallography provided GPCR molecular architectures, which also revealed the need for additional structural dynamics data to support drug development. Here, nuclear magnetic resonance (NMR) spectroscopy with the wild-type-like A adenosine receptor (AAR) in solution provides a comprehensive characterization of signaling-related structural dynamics. All six tryptophan indole and eight glycine backbone N-H NMR signals in AAR were individually assigned. These NMR probes provided insight into the role of Asp52 as an allosteric link between the orthosteric drug binding site and the intracellular signaling surface, revealing strong interactions with the toggle switch Trp 246, and delineated the structural response to variable efficacy of bound drugs across AAR. The present data support GPCR signaling based on dynamic interactions between two semi-independent subdomains connected by an allosteric switch at Asp52. PubMed: 29290469DOI: 10.1016/j.cell.2017.12.004 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.51 Å) |
Structure validation
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