8UWL
5-HT2AR bound to Lisuride in complex with a mini-Gq protein and an active-state stabilizing single-chain variable fragment (scFv16) obtained by cryo-electron microscopy (cryoEM)
Summary for 8UWL
| Entry DOI | 10.2210/pdb8uwl/pdb |
| EMDB information | 42676 |
| Descriptor | 5-hydroxytryptamine receptor 2A, G protein subunit q (Gi2-mini-Gq chimera), Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (6 entities in total) |
| Functional Keywords | 5-ht2a receptor, serotonin receptor, g protein, gpcr, lisuride, cryoem, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 142527.87 |
| Authors | Barros-Alvarez, X.,Kim, K.,Panova, O.,Roth, B.L.,Skiniotis, G. (deposition date: 2023-11-06, release date: 2024-05-29, Last modification date: 2024-11-13) |
| Primary citation | Lyu, J.,Kapolka, N.,Gumpper, R.,Alon, A.,Wang, L.,Jain, M.K.,Barros-Alvarez, X.,Sakamoto, K.,Kim, Y.,DiBerto, J.,Kim, K.,Glenn, I.S.,Tummino, T.A.,Huang, S.,Irwin, J.J.,Tarkhanova, O.O.,Moroz, Y.,Skiniotis, G.,Kruse, A.C.,Shoichet, B.K.,Roth, B.L. AlphaFold2 structures guide prospective ligand discovery. Science, 384:eadn6354-eadn6354, 2024 Cited by PubMed Abstract: AlphaFold2 (AF2) models have had wide impact but mixed success in retrospective ligand recognition. We prospectively docked large libraries against unrefined AF2 models of the σ and serotonin 2A (5-HT2A) receptors, testing hundreds of new molecules and comparing results with those obtained from docking against the experimental structures. Hit rates were high and similar for the experimental and AF2 structures, as were affinities. Success in docking against the AF2 models was achieved despite differences between orthosteric residue conformations in the AF2 models and the experimental structures. Determination of the cryo-electron microscopy structure for one of the more potent 5-HT2A ligands from the AF2 docking revealed residue accommodations that resembled the AF2 prediction. AF2 models may sample conformations that differ from experimental structures but remain low energy and relevant for ligand discovery, extending the domain of structure-based drug design. PubMed: 38753765DOI: 10.1126/science.adn6354 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.8 Å) |
Structure validation
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