A missense mutation in the seven-transmembrane domain of the human Ca2+ receptor converts a negative allosteric modulator into a positive allosteric modulator.

@article{Hu2006AMM,
  title={A missense mutation in the seven-transmembrane domain of the human Ca2+ receptor converts a negative allosteric modulator into a positive allosteric modulator.},
  author={Jianxin Hu and Jiankang Jiang and Stefano Costanzi and Craig Thomas and Wu Yang and Jean H M Feyen and Kenneth A. Jacobson and Allen M. Spiegel},
  journal={The Journal of biological chemistry},
  year={2006},
  volume={281 30},
  pages={21558-65}
}
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 lacks a response to previously described positive and negative modulators. A related… CONTINUE READING