6OBA
The beta2 adrenergic receptor bound to a negative allosteric modulator
Summary for 6OBA
| Entry DOI | 10.2210/pdb6oba/pdb |
| Descriptor | Beta-2 adrenergic receptor,Lysozyme,Beta-2 adrenergic receptor, CHOLESTEROL, (2S)-1-[(1-methylethyl)amino]-3-(2-prop-2-en-1-ylphenoxy)propan-2-ol, ... (4 entities in total) |
| Functional Keywords | g protein coupled receptors, signal transduction, allosteric modulators, membrane protein, signaling protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 57939.26 |
| Authors | Liu, X.,Stobel, A.,Kaindl, J.,Dengler, D.,ClarK, M.,Mahoney, J.,Korczynska, M.,Matt, R.A.,Hubner, H.,Xu, X.,Stanek, M.,Hirata, K.,Shoichet, B.,Sunahara, R.,Gmeiner, R.,Kobilka, B.K. (deposition date: 2019-03-20, release date: 2020-03-25, Last modification date: 2024-11-20) |
| Primary citation | Liu, X.,Kaindl, J.,Korczynska, M.,Stossel, A.,Dengler, D.,Stanek, M.,Hubner, H.,Clark, M.J.,Mahoney, J.,Matt, R.A.,Xu, X.,Hirata, K.,Shoichet, B.K.,Sunahara, R.K.,Kobilka, B.K.,Gmeiner, P. An allosteric modulator binds to a conformational hub in the beta2adrenergic receptor. Nat.Chem.Biol., 16:749-755, 2020 Cited by PubMed Abstract: Most drugs acting on G-protein-coupled receptors target the orthosteric binding pocket where the native hormone or neurotransmitter binds. There is much interest in finding allosteric ligands for these targets because they modulate physiologic signaling and promise to be more selective than orthosteric ligands. Here we describe a newly developed allosteric modulator of the β-adrenergic receptor (βAR), AS408, that binds to the membrane-facing surface of transmembrane segments 3 and 5, as revealed by X-ray crystallography. AS408 disrupts a water-mediated polar network involving E122 and the backbone carbonyls of V206 and S207. The AS408 binding site is adjacent to a previously identified molecular switch for βAR activation formed by I, P and F. The structure reveals how AS408 stabilizes the inactive conformation of this switch, thereby acting as a negative allosteric modulator for agonists and positive allosteric modulator for inverse agonists. PubMed: 32483378DOI: 10.1038/s41589-020-0549-2 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.1 Å) |
Structure validation
Download full validation report
