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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
