PDBsum entry 3vt7

Hormone receptor

PDB id: 3vt7

Contents

Protein chains

230 a.a.

11 a.a.

Ligands

VDX

Waters ×173

PDB id:

3vt7

Name:

Hormone receptor

Title:

Crystal structures of rat vdr-lbd with w282r mutation

Structure:

Vitamin d3 receptor. Chain: a. Fragment: unp residues 116-423. Synonym: vdr, 1,25-dihydroxyvitamin d3 receptor, nuclear receptor subfamily 1 group i member 1. Engineered: yes. Mutation: yes. Coactivator peptide drip. Chain: c.

Source:

Rattus norvegicus. Rats. Organism_taxid: 10116. Gene: nr1i1, vdr. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: peptide synthesis

Resolution:

1.65Å R-factor: 0.185 R-free: 0.229

Authors:

M.Nakabayashi,M.Shimizu,T.Ikura,N.Ito

Key ref:

M.Nakabayashi et al. (2013). 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. PubMed id: 23944708 DOI: 10.1021/jm400537h

Date:

19-May-12 Release date: 22-May-13

Protein chain

P13053  (VDR_RAT) -  Vitamin D3 receptor from Rattus norvegicus

Seq: 423 a.a.

Struc: 230 a.a.

Protein chain

D3ZRN2  (D3ZRN2_RAT) -  Mediator of RNA polymerase II transcription subunit 1 from Rattus norvegicus

Seq: 1568 a.a.

Struc: 11 a.a.

DOI no: 10.1021/jm400537h

J Med Chem 56:6745-6760 (2013)

PubMed id: 23944708

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.

M.Nakabayashi, Y.Tsukahara, Y.Iwasaki-Miyamoto, M.Mihori-Shimazaki, S.Yamada, S.Inaba, M.Oda, M.Shimizu, M.Makishima, H.Tokiwa, T.Ikura, N.Ito.

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.