9bs9
From Proteopedia
Local refinement of DRD2 bound to LSD in complex with a mini-GoA and scFv16 obtained by cryo-electron microscopy (cryoEM)
Structural highlights
DiseaseDRD2_HUMAN Myoclonic dystonia 11. The gene represented in this entry may be involved in disease pathogenesis. DRD2 mutations in myoclonic dystonia patients are rare, and their contribution to disease phenotype is unclear (PubMed:10716258). FunctionC562_ECOLX Electron-transport protein of unknown function.DRD2_HUMAN Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase (By similarity).[1] [2] Publication Abstract from PubMedThe classical psychedelics (+)-lysergic acid diethylamide (LSD), psilocybin, and mescaline exert their psychedelic effects via activation of the 5-HT(2A) serotonin receptor (5-HT(2A)R). 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-HT(2A)R 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. The polypharmacology of psychedelics reveals multiple targets for potential therapeutics.,Jain MK, Gumpper RH, Slocum ST, Schmitz GP, Madsen JS, Tummino TA, Suomivuori CM, Huang XP, Shub L, DiBerto JF, Kim K, DeLeon C, Krumm BE, Fay JF, Keiser M, Hauser AS, Dror RO, Shoichet B, Gloriam DE, Nichols DE, Roth BL Neuron. 2025 Jul 15:S0896-6273(25)00470-2. doi: 10.1016/j.neuron.2025.06.012. PMID:40683247[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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