Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Science 2010 Nov 19;330(6007):1091-5
Date
11/26/2010Pubmed ID
21097933Pubmed Central ID
PMC3058422DOI
10.1126/science.1197410Scopus ID
2-s2.0-78449305788 (requires institutional sign-in at Scopus site) 1045 CitationsAbstract
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.
Author List
Chien EY, Liu W, Zhao Q, Katritch V, Han GW, Hanson MA, Shi L, Newman AH, Javitch JA, Cherezov V, Stevens RCAuthor
Wei Liu PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsArginine
Binding Sites
Cell Line
Crystallography, X-Ray
Dopamine Antagonists
Dopamine D2 Receptor Antagonists
Humans
Models, Molecular
Protein Conformation
Receptors, Dopamine D3
Recombinant Proteins
Salicylamides
Spodoptera
