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PDBsum entry 3cs6

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protein ligands links
Gene regulation PDB id
3cs6
Jmol
Contents
Protein chain
254 a.a. *
Ligands
0CO
Waters ×193
* Residue conservation analysis
PDB id:
3cs6
Name: Gene regulation
Title: Structure-based design of a superagonist ligand for the vitamin d nuclear receptor
Structure: Vitamin d3 receptor. Chain: a. Fragment: unp residues 118-427. Synonym: vdr, 1,25-dihydroxyvitamin d3 receptor, nuclear receptor subfamily 1 group i member 1. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: vdr, nr1i1. Expressed in: escherichia coli.
Resolution:
1.80Å     R-factor:   0.192     R-free:   0.206
Authors: S.Hourai,L.C.Rodriguez,P.Antony,B.Reina-San-Martin, P.Ciesielski,B.C.Magnier,K.Schoonjans,A.Mourino,N.Rochel, D.Moras
Key ref: S.Hourai et al. (2008). Structure-based design of a superagonist ligand for the vitamin D nuclear receptor. Chem Biol, 15, 383-392. PubMed id: 18420145 DOI: 10.1016/j.chembiol.2008.03.016
Date:
09-Apr-08     Release date:   27-May-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P11473  (VDR_HUMAN) -  Vitamin D3 receptor
Seq:
Struc:
427 a.a.
254 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 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: 10.1016/j.chembiol.2008.03.016 Chem Biol 15:383-392 (2008)
PubMed id: 18420145  
 
 
Structure-based design of a superagonist ligand for the vitamin D nuclear receptor.
S.Hourai, L.C.Rodrigues, P.Antony, B.Reina-San-Martin, F.Ciesielski, B.C.Magnier, K.Schoonjans, A.Mouriño, N.Rochel, D.Moras.
 
  ABSTRACT  
 
Vitamin D nuclear receptor (VDR), a ligand-dependent transcriptional regulator, is an important target for multiple clinical applications, such as osteoporosis and cancer. Since exacerbated increase of calcium serum level is currently associated with VDR ligands action, superagonists with low calcium serum levels have been developed. Based on the crystal structures of human VDR (hVDR) bound to 1alpha,25-dihydroxyvitamin D(3) and superagonists-notably, KH1060-we designed a superagonist ligand. In order to optimize the aliphatic side chain conformation with a subsequent entropy benefit, we incorporated an oxolane ring and generated two stereo diasteromers, AMCR277A and AMCR277B. Only AMCR277A exhibits superagonist activity in vitro, but is as calcemic in vivo as the natural ligand. The crystal structures of the complexes between the ligand binding domain of hVDR and these ligands provide a rational approach to the design of more potent superagonist ligands for potential clinical application.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19961857 A.J.Annalora, D.B.Goodin, W.X.Hong, Q.Zhang, E.F.Johnson, and C.D.Stout (2010).
Crystal structure of CYP24A1, a mitochondrial cytochrome P450 involved in vitamin D metabolism.
  J Mol Biol, 396, 441-451.
PDB codes: 3k9v 3k9y
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