A5042702060- Drug Transport and Resistance Mechanisms
- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Coenzyme Q10 studies and effects
- Protein Hydrolysis and Bioactive Peptides
- Lipid Membrane Structure and Behavior
- Genomics, phytochemicals, and oxidative stress
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
Shanghai Institute of Materia Medica
2020-2021
National Center for Drug Screening
2020-2021
Takeda G protein-coupled receptor 5 (TGR5) is a promising target for treating metabolic syndrome and inflammatory diseases. Herein, we identified new series of betulinic acid derivatives as potent TGR5 agonists, which show remarkable activity on human (h) canine (c) but exhibit unpromising murine (m) TGR5. Species difference was also observed with many other reported agonists. Therefore, screened 29 amino acids were conserved in hTGR5 cTGR5 different mTGR5 found key acid, H88 (Y89 hTGR5),...
Abstract G protein-coupled bile acid receptor (GPBAR) is a membrane that senses acids to regulate diverse functions through Gs activation. Here, we report the cryo-EM structures of GPBAR–Gs complexes stabilized by either high-affinity P395 or semisynthesized derivative INT-777 at 3-Å resolution. These revealed large oval-shaped ligand pocket with several sporadic polar groups accommodate amphipathic cholic core acids. A fingerprint key residues recognizing in orthosteric site, putative...