PDB 1S19 deposited: 2004-01-06 modified: 2009-02-24
Title Crystal structure of VDR ligand binding domain complexed to calcipotriol.
Authors Moras, D., Rochel, N., Tocchini-Valentini, G., Wurtz, J.M.
Structure factors resolution 2.1 rfactor 0.179 rfree 0.214
DPI 0.42 theoretical min: 0.19
Related PDB Entries 1S0Z

The plethora of actions of 1alpha,25(OH)(2)D(3) in various systems suggested wide clinical applications of vitamin D nuclear receptor (VDR) ligands in treatments of inflammation, dermatological indication, osteoporosis, cancers, and autoimmune diseases. More than 3000 vitamin D analogues have been synthesized in order to reduce the calcemic side effects while maintaining the transactivation potency of these ligands. Here, we report the crystal structures of VDR ligand binding domain bound to two vitamin D agonists of therapeutical interest, calcipotriol and seocalcitol, which are characterized by their side chain modifications. These structures show the conservation of the VDR structure and the adaptation of the side chain anchored by hydroxyl moieties. The structure of VDR-calcipotriol helps us to understand the structural basis for for the switching of calcipotriol to a receptor antagonist by further side chain modification. The VDR-seocalcitol structure, in comparison with the structure of VDR-KH1060, a superagonist ligand closely related to seocalcitol, shows adaptation of the D ring and position of C-21 in order to adapt its more rigid side chain.

J.Med.Chem. 2004 Apr; 47(8):1956-1961 doi:10.1021/jm0310582

Cross References
Database source Identifier Description
ChEMBL Document CHEMBL1149141
PubMed 15055995 JMCMAR
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
1S19/0 1S19 0 monomer 0 1 1 2045