9BS9
Local refinement of DRD2 bound to LSD in complex with a mini-GoA and scFv16 obtained by cryo-electron microscopy (cryoEM)
Summary for 9BS9
| Entry DOI | 10.2210/pdb9bs9/pdb |
| EMDB information | 44865 |
| Descriptor | Soluble cytochrome b562,D(2) dopamine receptor, (8alpha)-N,N-diethyl-6-methyl-9,10-didehydroergoline-8-carboxamide (2 entities in total) |
| Functional Keywords | gpcr, g-protein coupled receptor, drd2, serotonin, psychedelics, membrane protein |
| Biological source | Escherichia coli More |
| Total number of polymer chains | 1 |
| Total formula weight | 67558.01 |
| Authors | Kim, K.,Gumpper, R.H.,Fay, J.F.,Roth, B.L. (deposition date: 2024-05-13, release date: 2025-09-17, Last modification date: 2025-10-15) |
| Primary citation | Jain, M.K.,Gumpper, R.H.,Slocum, S.T.,Schmitz, G.P.,Madsen, J.S.,Tummino, T.A.,Suomivuori, C.M.,Huang, X.P.,Shub, L.,DiBerto, J.F.,Kim, K.,DeLeon, C.,Krumm, B.E.,Fay, J.F.,Keiser, M.,Hauser, A.S.,Dror, R.O.,Shoichet, B.,Gloriam, D.E.,Nichols, D.E.,Roth, B.L. The polypharmacology of psychedelics reveals multiple targets for potential therapeutics. Neuron, 113:3129-3142.e9, 2025 Cited by PubMed Abstract: The classical psychedelics (+)-lysergic acid diethylamide (LSD), psilocybin, and mescaline exert their psychedelic effects via activation of the 5-HT serotonin receptor (5-HTR). Recent clinical studies have suggested that classical psychedelics may additionally have therapeutic potential for many neuropsychiatric conditions including depression, anxiety, migraine and cluster headaches, drug abuse, and post-traumatic stress disorder. In this study, we investigated the pharmacology of 41 classical psychedelics from the tryptamine, phenethylamine, and lysergamide chemical classes. We profiled these compounds against 318 human G-protein-coupled receptors (GPCRs) to elucidate their target profiles, and in the case of LSD, against more than 450 human kinases. We found that psychedelics have potent and efficacious actions at nearly every serotonin, dopamine, and adrenergic receptor. We quantified their activation for multiple transducers and found that psychedelics stimulate multiple 5-HTR transducers, each of which correlates with psychedelic drug-like actions in vivo. Our results suggest that multiple molecular targets likely contribute to the actions of psychedelics. PubMed: 40683247DOI: 10.1016/j.neuron.2025.06.012 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.28 Å) |
Structure validation
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