6N48
Structure of beta2 adrenergic receptor bound to BI167107, Nanobody 6B9, and a positive allosteric modulator
Summary for 6N48
Entry DOI | 10.2210/pdb6n48/pdb |
Descriptor | Endolysin,Beta-2 adrenergic receptor,Beta-2 adrenergic receptor chimera, Camelid Antibody Fragment, 8-[(1R)-2-{[1,1-dimethyl-2-(2-methylphenyl)ethyl]amino}-1-hydroxyethyl]-5-hydroxy-2H-1,4-benzoxazin-3(4H)-one, ... (5 entities in total) |
Functional Keywords | g protein coupled receptor, membrane protein, signaling protein |
Biological source | Enterobacteria phage RB59 More |
Total number of polymer chains | 2 |
Total formula weight | 67761.14 |
Authors | Liu, X.,Masoudi, A.,Kahsai, A.W.,Huang, L.Y.,Pani, B.,Hirata, K.,Ahn, S.,Lefkowitz, R.J.,Kobilka, B.K. (deposition date: 2018-11-17, release date: 2019-06-26, Last modification date: 2024-11-06) |
Primary citation | Liu, X.,Masoudi, A.,Kahsai, A.W.,Huang, L.Y.,Pani, B.,Staus, D.P.,Shim, P.J.,Hirata, K.,Simhal, R.K.,Schwalb, A.M.,Rambarat, P.K.,Ahn, S.,Lefkowitz, R.J.,Kobilka, B. Mechanism of beta2AR regulation by an intracellular positive allosteric modulator. Science, 364:1283-1287, 2019 Cited by PubMed Abstract: Drugs targeting the orthosteric, primary binding site of G protein-coupled receptors are the most common therapeutics. Allosteric binding sites, elsewhere on the receptors, are less well-defined, and so less exploited clinically. We report the crystal structure of the prototypic β-adrenergic receptor in complex with an orthosteric agonist and compound-6FA, a positive allosteric modulator of this receptor. It binds on the receptor's inner surface in a pocket created by intracellular loop 2 and transmembrane segments 3 and 4, stabilizing the loop in an α-helical conformation required to engage the G protein. Structural comparison explains the selectivity of the compound for β- over the β-adrenergic receptor. Diversity in location, mechanism, and selectivity of allosteric ligands provides potential to expand the range of receptor drugs. PubMed: 31249059DOI: 10.1126/science.aaw8981 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (3.2 Å) |
Structure validation
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