3M7R

Crystal structure of VDR H305Q mutant

Summary for 3M7R

• Entry DOI: 10.2210/pdb3m7r/pdb
• Related: 1DB1
• 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: ligand binding domain, transcription, structural genomics, spine, structural proteomics in europe
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : P11473
• Total number of polymer chains: 1
• Total formula weight: 29152.88

Authors

Rochel, N.,Hourai, S.,Moras, D.,Structural Proteomics in Europe (SPINE) (deposition date: 2010-03-17, release date: 2010-05-05, Last modification date: 2023-11-01)

Primary citation

Rochel, N.,Hourai, S.,Moras, D.
Crystal structure of hereditary vitamin D-resistant rickets--associated mutant H305Q of vitamin D nuclear receptor bound to its natural ligand
J.Steroid Biochem.Mol.Biol., 121:84-87, 2010

PubMed Abstract: In the nuclear receptor of vitamin D (VDR) histidine 305 participates to the anchoring of the ligand. The VDR H305Q mutation was identified in a patient who exhibited the hereditary vitamin D-resistant rickets (HVDRR). We report the crystal structure of human VDR H305Q-ligand binding domain bound to 1alpha,25(OH)2D3 solved at 1.8A resolution. The protein adopts the active conformation of the wild-type liganded VDR. A local conformational flexibility at the mutation site weakens the hydrogen bond between the 25-OH with Gln305, thus explaining the lower affinity of the mutant proteins for calcitriol. The structure provides the basis for a rational approach to the design of more potent ligands for the treatment of HVDRR.

PubMed: 20403435
DOI: 10.1016/j.jsbmb.2010.04.008

Experimental method

X-RAY DIFFRACTION (1.8 Å)