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Updated: Jan 31, 2026

Quantifying Agonist Activity at G Protein-coupled Receptors
Published on: December 26, 2011
Dual conformation of the ligand induces the partial agonistic activity of retinoid X receptor α (RXRα)
Yurina Miyashita1,2,3, Nobutaka Numoto3, Sundaram Arulmozhiraja1,4
1Department of Chemistry, Rikkyo University, Tokyo, Japan.
Abstract:
1-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino]benzotriazole-5-carboxylic acid (CBt-PMN), a partial agonist of retinoid X receptor (RXR), has attracted attention due to its potential to treat type 2 diabetes and central nervous system diseases with reduced adverse effects of existing full agonists. Herein, we report the crystal structure of CBt-PMN-bound ligand-binding domain of human RXRα (hRXRα) and its biochemical characterization. Interestingly, the structure is a tetramer in nature, in which CBt-PMNs are clearly found binding in two different conformations. The dynamics of the hRXRα/CBt-PMN complex examined using molecular dynamics simulations suggest that the flexibility of the AF-2 interface depends on the conformation of the ligand. These facts reveal that the dual conformation of CBt-PMN in the complex is probably the reason behind its partial agonistic activity.
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