Summary for 6MXT
| Entry DOI | 10.2210/pdb6mxt/pdb |
| Descriptor | Endolysin, Beta-2 adrenergic receptor chimera, nanobody Nb71, salmeterol, ... (10 entities in total) |
| Functional Keywords | g protein-coupled receptor, adrenergic receptor, asthma drug, active conformation, nanobody, signaling protein-hormone complex, membrane protein, signaling protein/hormone |
| Biological source | Enterobacteria phage T4 More |
| Total number of polymer chains | 2 |
| Total formula weight | 68731.36 |
| Authors | Masureel, M.,Zou, Y.,Picard, L.P.,van der Westhuizen, E.,Mahoney, J.P.,Rodrigues, J.P.G.L.M.,Mildorf, T.J.,Dror, R.O.,Shaw, D.E.,Bouvier, M.,Pardon, E.,Steyaert, J.,Sunahara, R.K.,Weis, W.I.,Zhang, C.,Kobilka, B.K. (deposition date: 2018-10-31, release date: 2018-11-14, Last modification date: 2023-10-11) |
| Primary citation | Masureel, M.,Zou, Y.,Picard, L.P.,van der Westhuizen, E.,Mahoney, J.P.,Rodrigues, J.P.G.L.M.,Mildorf, T.J.,Dror, R.O.,Shaw, D.E.,Bouvier, M.,Pardon, E.,Steyaert, J.,Sunahara, R.K.,Weis, W.I.,Zhang, C.,Kobilka, B.K. Structural insights into binding specificity, efficacy and bias of a beta2AR partial agonist. Nat. Chem. Biol., 14:1059-1066, 2018 Cited by PubMed Abstract: Salmeterol is a partial agonist for the β adrenergic receptor (βAR) and the first long-acting βAR agonist to be widely used clinically for the treatment of asthma and chronic obstructive pulmonary disease. Salmeterol's safety and mechanism of action have both been controversial. To understand its unusual pharmacological action and partial agonism, we obtained the crystal structure of salmeterol-bound βAR in complex with an active-state-stabilizing nanobody. The structure reveals the location of the salmeterol exosite, where sequence differences between βAR and βAR explain the high receptor-subtype selectivity. A structural comparison with the βAR bound to the full agonist epinephrine reveals differences in the hydrogen-bond network involving residues Ser204 and Asn293. Mutagenesis and biophysical studies suggested that these interactions lead to a distinct active-state conformation that is responsible for the partial efficacy of G-protein activation and the limited β-arrestin recruitment for salmeterol. PubMed: 30327561DOI: 10.1038/s41589-018-0145-x PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.95934213525 Å) |
Structure validation
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