1S19
Crystal structure of VDR ligand binding domain complexed to calcipotriol.
Summary for 1S19
| Entry DOI | 10.2210/pdb1s19/pdb |
| Related | 1DB1 1IE8 1IE9 1S0Z |
| Descriptor | Vitamin D3 receptor, CALCIPOTRIOL (3 entities in total) |
| Functional Keywords | nuclear receptor, transcription regulation, alpha-helical sandwich, gene regulation |
| Biological source | Homo sapiens (human) More |
| Cellular location | Nucleus: P11473 |
| Total number of polymer chains | 1 |
| Total formula weight | 30217.95 |
| Authors | Tocchini-Valentini, G.,Rochel, N.,Wurtz, J.M.,Moras, D. (deposition date: 2004-01-06, release date: 2004-04-13, Last modification date: 2024-02-14) |
| Primary citation | Tocchini-Valentini, G.,Rochel, N.,Wurtz, J.M.,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., 47:1956-1961, 2004 Cited by PubMed Abstract: 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. PubMed: 15055995DOI: 10.1021/jm0310582 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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