1IE9

Crystal Structure Of The Nuclear Receptor For Vitamin D Ligand Binding Domain Bound to MC1288

Summary for 1IE9

• Entry DOI: 10.2210/pdb1ie9/pdb
• Related: 1DB1 1IE8
• Descriptor: VITAMIN D3 RECEPTOR, 5-{2-[1-(5-HYDROXY-1,5-DIMETHYL-HEXYL)-7A-METHYL-OCTAHYDRO-INDEN-4-YLIDENE]-ETHYLIDENE}-4-METHYLENE-CYCLOHEXANE-1,3-DIOL (3 entities in total)
• Functional Keywords: vdr, mc1288, gene regulation
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P11473
• Total number of polymer chains: 1
• Total formula weight: 29808.51

Authors

Tocchini-Valentini, G.,Rochel, N.,Wurtz, J.M.,Mitschler, A.,Moras, D. (deposition date: 2001-04-09, release date: 2001-05-16, Last modification date: 2024-02-07)

Primary citation

Tocchini-Valentini, G.,Rochel, N.,Wurtz, J.M.,Mitschler, A.,Moras, D.
Crystal structures of the vitamin D receptor complexed to superagonist 20-epi ligands.
Proc.Natl.Acad.Sci.USA, 98:5491-5496, 2001

PubMed Abstract: The crystal structures of the ligand-binding domain (LBD) of the vitamin D receptor complexed to 1alpha,25(OH)(2)D(3) and the 20-epi analogs, MC1288 and KH1060, show that the protein conformation is identical, conferring a general character to the observation first made for retinoic acid receptor (RAR) that, for a given LBD, the agonist conformation is unique, the ligands adapting to the binding pocket. In all complexes, the A- to D-ring moieties of the ligands adopt the same conformation and form identical contacts with the protein. Differences are observed only for the 17beta-aliphatic chains that adapt their conformation to anchor the 25-hydroxyl group to His-305 and His-397. The inverted geometry of the C20 methyl group induces different paths of the aliphatic chains. The ligands exhibit a low-energy conformation for MC1288 and a more strained conformation for the two others. KH1060 compensates this energy cost by additional contacts. Based on the present data, the explanation of the superagonist effect is to be found in higher stability and longer half-life of the active complex, thereby excluding different conformations of the ligand binding domain.

PubMed: 11344298
DOI: 10.1073/pnas.091018698

Experimental method

X-RAY DIFFRACTION (1.4 Å)