7DFP

Human dopamine D2 receptor in complex with spiperone

Summary for 7DFP

• Entry DOI: 10.2210/pdb7dfp/pdb
• Descriptor: D(2) dopamine receptor,Soluble cytochrome b562, FabL, FabH, ... (4 entities in total)
• Functional Keywords: g-protein coupled receptor, dopamine receptor, spiperone, membrane protein, antipsychotic, schizophrenia
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 88313.55

Authors

Im, D.,Shimamura, T.,Iwata, S. (deposition date: 2020-11-09, release date: 2020-12-30, Last modification date: 2024-11-06)

Primary citation

Im, D.,Inoue, A.,Fujiwara, T.,Nakane, T.,Yamanaka, Y.,Uemura, T.,Mori, C.,Shiimura, Y.,Kimura, K.T.,Asada, H.,Nomura, N.,Tanaka, T.,Yamashita, A.,Nango, E.,Tono, K.,Kadji, F.M.N.,Aoki, J.,Iwata, S.,Shimamura, T.
Structure of the dopamine D 2 receptor in complex with the antipsychotic drug spiperone.
Nat Commun, 11:6442-6442, 2020

PubMed Abstract: In addition to the serotonin 5-HT receptor (5-HTR), the dopamine D receptor (DR) is a key therapeutic target of antipsychotics for the treatment of schizophrenia. The inactive state structures of DR have been described in complex with the inverse agonists risperidone (DR) and haloperidol (DR). Here we describe the structure of human DR in complex with spiperone (DR). In DR, the conformation of the extracellular loop (ECL) 2, which composes the ligand-binding pocket, was substantially different from those in DR and DR, demonstrating that ECL2 in DR is highly dynamic. Moreover, DR exhibited an extended binding pocket to accommodate spiperone's phenyl ring, which probably contributes to the selectivity of spiperone to DR and 5-HTR. Together with DR and DR, the structural information of DR should be of value for designing novel antipsychotics with improved safety and efficacy.

PubMed: 33353947
DOI: 10.1038/s41467-020-20221-0

Experimental method

X-RAY DIFFRACTION (3.1 Å)