Mapping of dopamine D3 receptor binding site by pharmacological characterization of mutants expressed in CHO cells with the Semliki Forest virus system

Journal of Receptor and Signal Transduction Research
K LundstromX Q Lewell

Abstract

Nine mutants and the wild-type human dopamine D3 receptor were expressed at high levels in BHK and CHO cells using the Semliki Forest virus system and were analysed for receptor binding with several structurally different dopamine D3 ligands. The mutation His349Leu showed a significant decrease in pKi values for raclopride, dopamine and GR218231, but an increase in affinity for GR99841. Thr369Val had an increase in pKi for both GR99841 and 7-OH-DPAT. The receptor modelling based on sequence alignment with bacteriorhodopsin indicated that Thr369 and His349 are located on the inside of the ligand binding pocket and the effect of the mutagenesis was therefore expected. The change in binding affinity for Thr369Val could be due to the location in the transmembrane domain VII close to the aspartate residue in domain III, the postulated counter ion for dopamine.

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Citations

Jun 25, 2013·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Shinichiro NakajimaAriel Graff-Guerrero
Oct 25, 2000·Insect Biochemistry and Molecular Biology·P V PietrantonioT K Hayesa
May 17, 2012·The Journal of Pharmacology and Experimental Therapeutics·Spencer S EricksenJohn A Schetz
Jan 25, 2002·Annual Review of Pharmacology and Toxicology·Lei Shi, Jonathan A Javitch
May 27, 2004·Proteins·Paul R GouldsonChristopher A Reynolds
Oct 29, 2014·Journal of Chemical Information and Modeling·Miwa Sato, Takatsugu Hirokawa
Mar 21, 2008·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Igor BombinAna Patiño-Garcia
Mar 11, 1999·Journal of Receptor and Signal Transduction Research·K Lundstrom
Sep 26, 2019·General Psychiatry·Lei Cai, Lin He
May 30, 2013·British Journal of Pharmacology·A J KooistraC de Graaf
Nov 11, 2005·Journal of Medicinal Chemistry·Scott OloffAlexander Tropsha
Aug 11, 2010·Journal of Chemical Information and Modeling·Yaxue ZhaoJian Zhang
Nov 26, 2010·Journal of Chemical Information and Modeling·Gabriella OrtoreAdriano Martinelli
Oct 24, 2018·Journal of Medicinal Chemistry·Márton VassChris de Graaf

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