PDBsum entry 7dfp

Membrane protein

PDB id: 7dfp

Contents

Protein chains

335 a.a.

215 a.a.

220 a.a.

Ligands

SIP

PDB id:

7dfp

Name:

Membrane protein

Title:

Human dopamine d2 receptor in complex with spiperone

Structure:

D(2) dopamine receptor,soluble cytochrome b562. Chain: a. Synonym: dopamine d2 receptor,cytochrome b-562,cytochrome b-562, dopamine d2 receptor. Engineered: yes. Mutation: yes. Other_details: chimera protein of residues 35-220 from d(2) dopamine receptor, residues 23-62 and 88-128 from soluble cytochrome b562, residues 364-443 from d(2) dopamine receptor..

Source:

Homo sapiens, escherichia coli. Human. Organism_taxid: 9606, 562. Gene: drd2, cybc. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Mus musculus. Organism_taxid: 10090. Organism_taxid: 10090

Resolution:

3.10Å R-factor: 0.187 R-free: 0.217

Authors:

D.Im,T.Shimamura,S.Iwata

Key ref:

D.Im et al. (2020). Structure of the dopamine D₂ receptor in complex with the antipsychotic drug spiperone. Nat Commun, 11, 6442. PubMed id: 33353947 DOI: 10.1038/s41467-020-20221-0

Date:

09-Nov-20 Release date: 30-Dec-20

Protein chain

P0ABE7  (C562_ECOLX) -  Soluble cytochrome b562 from Escherichia coli

Seq: 128 a.a.

Struc: 335 a.a.*

Protein chain

P14416  (DRD2_HUMAN) -  D(2) dopamine receptor from Homo sapiens

Seq: 443 a.a.

Struc: 335 a.a.*

Protein chain

No UniProt id for this chain

Struc: 215 a.a.

Protein chain

No UniProt id for this chain

Struc: 220 a.a.

* PDB and UniProt seqs differ at 90 residue positions (black crosses)

DOI no: 10.1038/s41467-020-20221-0

Nat Commun 11:6442 (2020)

PubMed id: 33353947

Structure of the dopamine D₂ receptor in complex with the antipsychotic drug spiperone.

D.Im, A.Inoue, T.Fujiwara, T.Nakane, Y.Yamanaka, T.Uemura, C.Mori, Y.Shiimura, K.T.Kimura, H.Asada, N.Nomura, T.Tanaka, A.Yamashita, E.Nango, K.Tono, F.M.N.Kadji, J.Aoki, S.Iwata, T.Shimamura.

ABSTRACT

In addition to the serotonin 5-HT_2A receptor (5-HT_2AR), the dopamine D₂ receptor (D₂R) is a key therapeutic target of antipsychotics for the treatment of schizophrenia. The inactive state structures of D₂R have been described in complex with the inverse agonists risperidone (D₂R_ris) and haloperidol (D₂R_hal). Here we describe the structure of human D₂R in complex with spiperone (D₂R_spi). In D₂R_spi, the conformation of the extracellular loop (ECL) 2, which composes the ligand-binding pocket, was substantially different from those in D₂R_ris and D₂R_hal, demonstrating that ECL2 in D₂R is highly dynamic. Moreover, D₂R_spi exhibited an extended binding pocket to accommodate spiperone's phenyl ring, which probably contributes to the selectivity of spiperone to D₂R and 5-HT_2AR. Together with D₂R_ris and D₂R_hal, the structural information of D₂R_spi should be of value for designing novel antipsychotics with improved safety and efficacy.