7WC9
Crystal structure of serotonin 2A receptor in complex with non-hallucinogenic psychedelic analog
Summary for 7WC9
| Entry DOI | 10.2210/pdb7wc9/pdb |
| Descriptor | 5-hydroxytryptamine receptor 2A,5-hydroxytryptamine receptor 2A,Soluble cytochrome b562, MAGNESIUM ION, CHOLESTEROL, ... (8 entities in total) |
| Functional Keywords | serotonin 2a receptor, non-hallucinogenic psychedelic, membrane protein, serotonin, 5-ht |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 46207.80 |
| Authors | |
| Primary citation | Cao, D.,Yu, J.,Wang, H.,Luo, Z.,Liu, X.,He, L.,Qi, J.,Fan, L.,Tang, L.,Chen, Z.,Li, J.,Cheng, J.,Wang, S. Structure-based discovery of nonhallucinogenic psychedelic analogs. Science, 375:403-411, 2022 Cited by PubMed Abstract: Drugs that target the human serotonin 2A receptor (5-HTR) are used to treat neuropsychiatric diseases; however, many have hallucinogenic effects, hampering their use. Here, we present structures of 5-HTR complexed with the psychedelic drugs psilocin (the active metabolite of psilocybin) and d-lysergic acid diethylamide (LSD), as well as the endogenous neurotransmitter serotonin and the nonhallucinogenic psychedelic analog lisuride. Serotonin and psilocin display a second binding mode in addition to the canonical mode, which enabled the design of the psychedelic IHCH-7113 (a substructure of antipsychotic lumateperone) and several 5-HTR β-arrestin-biased agonists that displayed antidepressant-like activity in mice but without hallucinogenic effects. The 5-HTR complex structures presented herein and the resulting insights provide a solid foundation for the structure-based design of safe and effective nonhallucinogenic psychedelic analogs with therapeutic effects. PubMed: 35084960DOI: 10.1126/science.abl8615 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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