Work

Structure of the Human Dopamine D3 Receptor in Complex with a D2/D3 Selective Antagonist

Year: 2010

Type: article

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.

Source: Science

DOI: 10.1126/science.1197410

Authors: Ellen Y. T. Chien, Wei Liu, Qiang Zhao, Vsevolod Katritch, Gye Won Han, Michael A. Hanson, Lei Shi, Amy Hauck Newman, Jonathan A. Javitch, Vadim Cherezov, Raymond C. Stevens

Institutions: Scripps Research Institute, San Diego Supercomputer Center, University of California San Diego, Cornell University, Weill Cornell Medicine, National Institute on Drug Abuse, Columbia University

Language: English

Topic: Receptor Mechanisms and Signaling

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Institute of General Medical Sciences, National Center for Research Resources

Awards: G1400479227, G1550356504, G1578358494, G1766531844, Membrane Proteins, Crystallogenesis and X-ray Structure, G2363639003, Molecular determinants for the action of psychostimulants, G3284996578, The Neurotransmitter: Sodium Symporter Permeation Pathway, G3925135328, G402281873, G521840061, Gene to Structure for $10K (GTS10K), JCIMPT-Complexes, G66439552, Structure and Function of Dopamine Receptors, G94731328

OpenAlex ID: W2104961861

FWCI: 52.56

Cites: 37

Cited by: 1,129

Related to: 10