6A94
Crystal structure of 5-HT2AR in complex with zotepine
Summary for 6A94
| Entry DOI | 10.2210/pdb6a94/pdb |
| Descriptor | 5-hydroxytryptamine receptor 2A,Soluble cytochrome b562, 2-(3-chloranylbenzo[b][1]benzothiepin-5-yl)oxy-N,N-dimethyl-ethanamine, CHOLESTEROL, ... (7 entities in total) |
| Functional Keywords | receptor, membrane protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 86215.78 |
| Authors | Kimura, T.K.,Asada, H.,Inoue, A.,Kadji, F.M.N.,Im, D.,Mori, C.,Arakawa, T.,Hirata, K.,Nomura, Y.,Nomura, N.,Aoki, J.,Iwata, S.,Shimamura, T. (deposition date: 2018-07-11, release date: 2019-02-13, Last modification date: 2024-10-23) |
| Primary citation | Kimura, K.T.,Asada, H.,Inoue, A.,Kadji, F.M.N.,Im, D.,Mori, C.,Arakawa, T.,Hirata, K.,Nomura, Y.,Nomura, N.,Aoki, J.,Iwata, S.,Shimamura, T. Structures of the 5-HT2Areceptor in complex with the antipsychotics risperidone and zotepine. Nat.Struct.Mol.Biol., 26:121-128, 2019 Cited by PubMed Abstract: Many drugs target the serotonin 2A receptor (5-HTR), including second-generation antipsychotics that also target the dopamine D receptor (DR). These drugs often produce severe side effects due to non-selective binding to other aminergic receptors. Here, we report the structures of human 5-HTR in complex with the second-generation antipsychotics risperidone and zotepine. These antipsychotics effectively stabilize the inactive conformation by forming direct contacts with the residues at the bottom of the ligand-binding pocket, the movements of which are important for receptor activation. 5-HTR is structurally similar to 5-HTR but possesses a unique side-extended cavity near the orthosteric binding site. A docking study and mutagenic studies suggest that a highly 5-HTR-selective antagonist binds the side-extended cavity. The conformation of the ligand-binding pocket in 5-HTR significantly differs around extracellular loops 1 and 2 from that in DR. These findings are beneficial for the rational design of safer antipsychotics and 5-HTR-selective drugs. PubMed: 30723326DOI: 10.1038/s41594-018-0180-z PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.9 Å) |
Structure validation
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