PDB 1IE9 deposited: 2001-04-09 modified: 2009-02-24
Title Crystal Structure Of The Nuclear Receptor For Vitamin D Ligand Binding Domain Bound to MC1288
Authors Mitschler, A., Moras, D., Rochel, N., Tocchini-Valentini, G., Wurtz, J.M.
Structure factors resolution 1.4 rfactor 0.214 rfree 0.248
DPI 0.24 theoretical min: 0.08
Related PDB Entries 1IE8

The crystal structures of the ligand-binding domain (LBD) of the vitamin D receptor complexed to 1alpha,25(OH)(2)D(3) and the 20-epi analogs, MC1288 and KH1060, show that the protein conformation is identical, conferring a general character to the observation first made for retinoic acid receptor (RAR) that, for a given LBD, the agonist conformation is unique, the ligands adapting to the binding pocket. In all complexes, the A- to D-ring moieties of the ligands adopt the same conformation and form identical contacts with the protein. Differences are observed only for the 17beta-aliphatic chains that adapt their conformation to anchor the 25-hydroxyl group to His-305 and His-397. The inverted geometry of the C20 methyl group induces different paths of the aliphatic chains. The ligands exhibit a low-energy conformation for MC1288 and a more strained conformation for the two others. KH1060 compensates this energy cost by additional contacts. Based on the present data, the explanation of the superagonist effect is to be found in higher stability and longer half-life of the active complex, thereby excluding different conformations of the ligand binding domain.

Proc.Natl.Acad.Sci.USA 2001 May; 98(10):5491-5496 doi:10.1073/pnas.091018698

Cross References
Database source Identifier Description
PubMed 11344298 PNASA6
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
1IE9/0 1IE9 0 monomer 0 1 1 2095