3PBL

Structure of the human dopamine D3 receptor in complex with eticlopride

Summary for 3PBL

• Entry DOI: 10.2210/pdb3pbl/pdb
• Related PRD ID: PRD_900001
• Descriptor: D(3) dopamine receptor, Lysozyme chimera, alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, 3-chloro-5-ethyl-N-{[(2S)-1-ethylpyrrolidin-2-yl]methyl}-6-hydroxy-2-methoxybenzamide (3 entities in total)
• Functional Keywords: structural genomics, psi-2, psi-biology, protein structure initiative, accelerated technologies center for gene to 3d structure, atcg3d, 7tm, g protein-coupled receptor, gpcr, gpcr network, signal transduction, hydrolase, eticlopride, dopamine, neurotransmitter, chimera, t4l fusion, membrane protein, transmembrane, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human, Bacteriophage T4); More
• Total number of polymer chains: 2
• Total formula weight: 108672.38

Authors

Chien, E.Y.T.,Liu, W.,Han, G.W.,Katritch, V.,Zhao, Q.,Cherezov, V.,Stevens, R.C.,Accelerated Technologies Center for Gene to 3D Structure (ATCG3D),GPCR Network (GPCR) (deposition date: 2010-10-20, release date: 2010-11-03, Last modification date: 2024-10-16)

Primary citation

Chien, E.Y.,Liu, W.,Zhao, Q.,Katritch, V.,Han, G.W.,Hanson, M.A.,Shi, L.,Newman, A.H.,Javitch, J.A.,Cherezov, V.,Stevens, R.C.
Structure of the human dopamine d3 receptor in complex with a d2/d3 selective antagonist.
Science, 330:1091-1095, 2010

PubMed Abstract: Dopamine modulates movement, cognition, and emotion through activation of dopamine G protein-coupled receptors in the brain. The crystal structure of the human dopamine D3 receptor (D3R) in complex with the small molecule D2R/D3R-specific antagonist eticlopride reveals important features of the ligand binding pocket and extracellular loops. On the intracellular side of the receptor, a locked conformation of the ionic lock and two distinctly different conformations of intracellular loop 2 are observed. Docking of R-22, a D3R-selective antagonist, reveals an extracellular extension of the eticlopride binding site that comprises a second binding pocket for the aryl amide of R-22, which differs between the highly homologous D2R and D3R. This difference provides direction to the design of D3R-selective agents for treating drug abuse and other neuropsychiatric indications.

PubMed: 21097933
DOI: 10.1126/science.1197410

Experimental method

X-RAY DIFFRACTION (2.89 Å)