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PDBsum entry 3vt4

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protein ligands Protein-protein interface(s) links
Hormone receptor PDB id
3vt4
Jmol
Contents
Protein chains
240 a.a.
11 a.a.
Ligands
5YI
Waters ×108
PDB id:
3vt4
Name: Hormone receptor
Title: Crystal structures of rat vdr-lbd with r270l mutation
Structure: Vitamin d3 receptor. Chain: a. Fragment: unp residues 116-423. Synonym: vdr, 1,25-dihydroxyvitamin d3 receptor, nuclear re 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:
1.90Å     R-factor:   0.212     R-free:   0.260
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    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P13053  (VDR_RAT) -  Vitamin D3 receptor
Seq:
Struc:
423 a.a.
240 a.a.*
Protein chain
No UniProt id for this chain
Struc: 11 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     steroid hormone mediated signaling pathway   2 terms 
  Biochemical function     DNA binding     4 terms  

 

 
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.