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1s0z
From Proteopedia
Crystal structure of the VDR LBD complexed to seocalcitol.
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.
Crystal structures of the vitamin D nuclear receptor liganded with the vitamin D side chain analogues calcipotriol and seocalcitol, receptor agonists of clinical importance. Insights into a structural basis for the switching of calcipotriol to a receptor antagonist by further side chain modification., Tocchini-Valentini G, Rochel N, Wurtz JM, Moras D, J Med Chem. 2004 Apr 8;47(8):1956-61. PMID:15055995
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1S0Z is a 1 chain structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Tocchini-Valentini G, Rochel N, Wurtz JM, Moras D. Crystal structures of the vitamin D nuclear receptor liganded with the vitamin D side chain analogues calcipotriol and seocalcitol, receptor agonists of clinical importance. Insights into a structural basis for the switching of calcipotriol to a receptor antagonist by further side chain modification. J Med Chem. 2004 Apr 8;47(8):1956-61. PMID:15055995 doi:10.1021/jm0310582
Page seeded by OCA on Mon Feb 16 21:27:44 2009
