Dopamine D₂ Receptor Agonist Binding Kinetics-Role of a Conserved Serine Residue.

ABSTRACT: The forward (k_on) and reverse (k_off) rate constants of drug-target interactions have important implications for therapeutic efficacy. Hence, time-resolved assays capable of measuring these binding rate constants may be informative to drug discovery efforts. Here, we used an ion channel activation assay to estimate the k_ons and k_offs of four dopamine D₂ receptor (D₂R) agonists; dopamine (DA), p-tyramine, (R)- and (S)-5-OH-dipropylaminotetralin (DPAT). We further probed the role of the conserved serine S193^5.42 by mutagenesis, taking advantage of the preferential interaction of (S)-, but not (R)-5-OH-DPAT with this residue. Results suggested similar k_offs for the two 5-OH-DPAT enantiomers at wild-type (WT

SUBMITTER: Agren R 

PROVIDER: S-EPMC8071183 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature