In:
FEBS Letters, Wiley, Vol. 593, No. 2 ( 2019-01), p. 242-250
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 CB t‐ PMN ‐bound ligand‐binding domain of human RXR α ( hRXR α) and its biochemical characterization. Interestingly, the structure is a tetramer in nature, in which CB t‐ PMN s are clearly found binding in two different conformations. The dynamics of the hRXR α/ CB t‐ 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 CB t‐ PMN in the complex is probably the reason behind its partial agonistic activity.
Type of Medium:
Online Resource
ISSN:
0014-5793
,
1873-3468
DOI:
10.1002/feb2.2019.593.issue-2
DOI:
10.1002/1873-3468.13301
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
1460391-3
SSG:
12
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