3KPZ

Crystal structure of a novel vitamin D3 analogue, ZK203278 showing dissociated profile

Summary for 3KPZ

• Entry DOI: 10.2210/pdb3kpz/pdb
• Related: 1DB1 1IE8 1IE9
• Descriptor: Vitamin D3 receptor, (1R,3S,5Z)-5-[(2E)-2-{(1R,3aS,7aR)-1-[(1R,5S)-5-hydroxy-1-methyl-5-(1,3-thiazol-2-yl)pentyl]-7a-methyloctahydro-4H-inden-4-ylidene}ethylidene]-4-methylidenecyclohexane-1,3-diol (3 entities in total)
• Functional Keywords: nuclear receptor, agonist, dna-binding, transcription regulation, transcription-hormone complex, transcription/hormone
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P11473
• Total number of polymer chains: 1
• Total formula weight: 29863.57

Authors

Rochel, N.,Moras, D. (deposition date: 2009-11-17, release date: 2011-10-12, Last modification date: 2023-09-06)

Primary citation

Rochel, N.,Moras, D.
Crystal structure of a vitamin D3 analog, ZK203278, showing dissociated profile.
Anticancer Res., 32:335-339, 2012

PubMed Abstract: The plethora of actions of 1α,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/1α,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.

PubMed: 22213324

Experimental method

X-RAY DIFFRACTION (1.9 Å)