3VT3

Crystal structures of rat VDR-LBD with R270L mutation

Summary for 3VT3

• Entry DOI: 10.2210/pdb3vt3/pdb
• Related: 2ZLC 3VT4 3VT5 3VT6 3VT7 3VT8 3VT9
• Descriptor: Vitamin D3 receptor, COACTIVATOR PEPTIDE DRIP, 5-{2-[1-(5-HYDROXY-1,5-DIMETHYL-HEXYL)-7A-METHYL-OCTAHYDRO-INDEN-4-YLIDENE]-ETHYLIDENE}-4-METHYLENE-CYCLOHEXANE-1,3-DIOL, ... (6 entities in total)
• Functional Keywords: transcription, hormone receptor
• Biological source: Rattus norvegicus (rats); More
• Cellular location: Nucleus: P13053
• Total number of polymer chains: 2
• Total formula weight: 32692.65

Authors

Nakabayashi, M.,Shimizu, M.,Ikura, T.,Ito, N. (deposition date: 2012-05-19, release date: 2013-05-22, Last modification date: 2023-11-08)

Primary citation

Nakabayashi, M.,Tsukahara, Y.,Iwasaki-Miyamoto, Y.,Mihori-Shimazaki, M.,Yamada, S.,Inaba, S.,Oda, M.,Shimizu, M.,Makishima, M.,Tokiwa, H.,Ikura, T.,Ito, N.
Crystal structures of hereditary vitamin D-resistant rickets-associated vitamin D receptor mutants R270L and W282R bound to 1,25-dihydroxyvitamin D3 and synthetic ligands.
J.Med.Chem., 56:6745-6760, 2013

PubMed Abstract: The vitamin D receptor (VDR), a member of the nuclear receptor superfamily, functions as a ligand-dependent transcription factor for various genes. Hereditary vitamin D-resistant rickets (HVDRR), an autosomal recessive disease, is caused by mutations in the VDR. In particular, the missense mutations R274L and W286R in the ligand-binding domain of the VDR can severely reduce or even eliminate natural hormone responsiveness. Here, we report a crystal structure analysis of the R270L and W282R mutants of rat VDR (human R274L and W286R, respectively) in complex with the natural hormone and synthetic ligands. We also studied the folding properties of the mutant proteins by using circular dichroism spectra. Our study indicates that these mutations result in only local structural modifications. We discuss why these mutations disrupt the VDR function and provide clues to develop effective ligands for the treatment of HVDRR.

PubMed: 23944708
DOI: 10.1021/jm400537h

Experimental method

X-RAY DIFFRACTION (1.7 Å)