Article
A missense mutation in the seven-transmembrane domain of the human Ca2+ receptor converts a negative allosteric modulator into a positive allosteric modulator.
The Journal of biological chemistry - 28 Jul 2006
Hu Jianxin, Jiang Jiankang, Costanzi Stefano, Thomas Craig, Yang Wu, Feyen Jean H M, Jacobson Kenneth A, Spiegel Allen M
Abstract excerpt
G protein-coupled receptors (GPCRs) are the most common targets of drug action. Allosteric modulators bind to the seven-transmembrane domain of family 3 GPCRs and offer enhanced selectivity over orthosteric ligands that bind to the large extracellular N terminus. We characterize a novel negative allosteric modulator of the human Ca(2+) receptor, Compound 1, that retains activity against the E837A mutant that...
Topics
- Allosteric Site
- Calcium
- Cell Line
- Glutamic Acid
- Humans
- Hydrolysis
- Ligands
- Models, Chemical
- Models, Molecular
- Mutation
- Mutation, Missense