5WF6
Agonist bound human A2a adenosine receptor with S91A mutation at 2.90 A resolution
Summary for 5WF6
| Entry DOI | 10.2210/pdb5wf6/pdb |
| Descriptor | Human A2a adenosine receptor T4L chimera, 6-(2,2-diphenylethylamino)-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxy-oxolan-2-yl]-N-[2-[(1-pyridin-2-ylpiperidin-4-yl)carbamoylamino]ethyl]purine-2-carboxamide, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, ... (4 entities in total) |
| Functional Keywords | human a2a adenosine receptor, s91a, gpcr-t4l chimera, membrane protein, lcp, agonist, uk432097, activation microswitch, allosteric na-site mutant, gpcr signaling |
| Biological source | Homo sapiens (Human) More |
| Cellular location | Cell membrane; Multi-pass membrane protein: P29274 |
| Total number of polymer chains | 1 |
| Total formula weight | 57674.47 |
| Authors | White, K.L.,Eddy, M.T.,Gao, Z.,Han, G.W.,Hanson, M.A.,Lian, T.,Deary, A.,Patel, N.,Jacobson, K.A.,Katritch, V.,Stevens, R.C. (deposition date: 2017-07-11, release date: 2018-02-21, Last modification date: 2024-10-16) |
| Primary citation | White, K.L.,Eddy, M.T.,Gao, Z.G.,Han, G.W.,Lian, T.,Deary, A.,Patel, N.,Jacobson, K.A.,Katritch, V.,Stevens, R.C. Structural Connection between Activation Microswitch and Allosteric Sodium Site in GPCR Signaling. Structure, 26:259-269.e5, 2018 Cited by PubMed Abstract: Sodium ions are endogenous allosteric modulators of many G-protein-coupled receptors (GPCRs). Mutation of key residues in the sodium binding motif causes a striking effect on G-protein signaling. We report the crystal structures of agonist complexes for two variants in the first sodium coordination shell of the human A adenosine receptor, D52N and S91A. Both structures present an overall active-like conformation; however, the variants show key changes in the activation motif NPxxY. Changes in the hydrogen bonding network in this microswitch suggest a possible mechanism for modified G-protein signaling and enhanced thermal stability. These structures, signaling data, and thermal stability analysis with a panel of pharmacological ligands provide a basis for understanding the role of the sodium-coordinating residues on stability and G-protein signaling. Utilizing the DN variant is a promising method for stabilizing class A GPCRs to accelerate structural efforts and drug discovery. PubMed: 29395784DOI: 10.1016/j.str.2017.12.013 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.9 Å) |
Structure validation
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