3KPZ: Crystal Structure Of A Novel Vitamin D3 Analogue, Zk203278 Showing Dissociated Profile

Citation:
Abstract
The plethora of actions of 1alpha,25-dihydroxyvitamin D(3), the active form of the seco-steroid hormone vitamin D, in various systems suggested wide clinical applications in treatments for renal osteodystrophy, osteoporosis, psoriasis, cancer, autoimmune diseases and prevention of graft rejection. However, the major side-effects of hypercalcemia of VDR ligands limit their use. ZK203278, a novel synthetic analog has been shown to act as a potent immunomodulator and presents dissociated biologic profile with low calcemic side-effects. Here, we described the crystal structures of the hVDR ligand-binding domain in complex with ZK203278 and determined its correlation with its specific dissociated biologic profile. The VDR/ZK203278 structure, in comparison with VDR/1alpha,25-dihydroxyvitamin D(3), shows specific interactions of the thiazole group of ZK203278 with residues of H3, H11 and H12. These specific interactions may lead to altered selective interactions with co-regulators and consequently to the dissociated biologic profile of this novel ligand.
PDB ID: 3KPZDownload
MMDB ID: 94202
PDB Deposition Date: 2009/11/17
Updated in MMDB: 2011/10
Experimental Method:
x-ray diffraction
Resolution: 1.9  Å
Source Organism:
Similar Structures:
Biological Unit for 3KPZ: monomeric; determined by author and by software (PISA)
Molecular Components in 3KPZ
Label Count Molecule
Protein (1 molecule)
1
Vitamin D3 Receptor(Gene symbol: VDR)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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