Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist

Science

Volumn 330, Issue 6007, 2010, Pages 1091-1095

  Chien, Ellen Y T ^a   Liu, Wei ^a   Zhao, Qiang ^a   Katritch, Vsevolod ^b   Han, Gye Won ^a   Hanson, Michael A ^c   Shi, Lei ^d   Newman, Amy Hauck ^e   Javitch, Jonathan A ^f   Cherezov, Vadim ^a   Stevens, Raymond C ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^c Receptos   (United States)

^d WEILL CORNELL MEDICAL COLLEGE   (United States)

^e NATIONAL INSTITUTE ON DRUG ABUSE   (United States)

^f Columbia University College of Physicians and Surgeons ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AROMATIC AMIDE; DOPAMINE 3 RECEPTOR; ETICLOPRIDE; G PROTEIN COUPLED RECEPTOR;

BRAIN; COGNITION; CRYSTAL STRUCTURE; ION; LIGAND; MOLECULAR ANALYSIS; MOVEMENT; NEUROLOGY; PROTEIN;

ARTICLE; COGNITION; CRYSTAL STRUCTURE; DRUG ABUSE; DRUG BINDING SITE; DRUG INDICATION; EMOTION; HUMAN; LIGAND BINDING; MOLECULAR DOCKING; PRIORITY JOURNAL;

ANIMALS; ARGININE; BINDING SITES; CELL LINE; CRYSTALLOGRAPHY, X-RAY; DOPAMINE ANTAGONISTS; HUMANS; MODELS, MOLECULAR; PROTEIN CONFORMATION; RECEPTORS, DOPAMINE D2; RECEPTORS, DOPAMINE D3; RECOMBINANT PROTEINS; SALICYLAMIDES; SPODOPTERA;

EID: 78449305788     PISSN: 00368075     EISSN: 10959203     Source Type: Journal    
DOI: 10.1126/science.1197410     Document Type: Article

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43. This work was supported in part by Protein Structure Initiative (PSI) grant U54 GM074961 and PSI:Biology grant U54 GM094618 for structure production, NIH Roadmap grant P50 GM073197 for technology development, NIH grant R21 RR025336 (V.C.), and Pfizer. Additional support was provided by the National Institute on Drug Abuse Intramural Research Program (A.H.N.), grants DA022413 and MH54137 (J.A.J.), and grant DA023694 (L.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Science or the NIH. We thank J. Velasquez for help with molecular biology, T. Trinh and K. Allin for help with baculovirus expression, D. Gray for assistance with eticlopride synthesis, M. Griffor for large-scale production of the receptor, X. Qiu for suggestions, and A. Walker for assistance with manuscript preparation. We acknowledge Y. Zheng, The Ohio State University and M. Caffrey, Trinity College (Dublin, Ireland), for the generous loan of the in meso robot (built with support from NIH grant GM075915), the National Science Foundation (grant IIS0308078), and Science Foundation Ireland (grant 02-IN1-B266); and J. Smith, R. Fischetti, and N. Sanishvili at the GM/CA-CAT beamline at the Advanced Photon Source, for assistance in development and use of the minibeam and beamtime. The GM/CA-CAT beamline (23-ID) is supported by the National Cancer Institute (grant Y1-CO-1020) and the National Institute of General Medical Sciences (grant Y1-GM-1104). Atomic coordinates and structure factors have been deposited in the Protein Data Bank with identification code 3PBL. A.H.N. is an inventor on a patent application from the National Institutes of Health that covers the use of R-22 and analogs as D3 receptor selective agents. R.C.S. is on the Board of Directors of Receptos, which does structure-directed drug discovery on GPCRs.