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PDBsum entry 3cs4
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Gene regulation
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PDB id
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3cs4
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Contents |
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* Residue conservation analysis
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PDB id:
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| Name: |
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Gene regulation
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Title:
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Structure-based design of a superagonist ligand for the vitamin d nuclear receptor
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Structure:
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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
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: vdr, nr1i1. Expressed in: escherichia coli.
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Resolution:
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2.00Å
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R-factor:
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0.186
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R-free:
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0.217
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Authors:
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S.Hourai,L.C.Rodriguez,P.Antony,B.Reina-San-Martin,F.Ciesielski, B.C.Magnier,K.Schoonjans,A.Mourino,N.Rochel,D.Moras
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Key ref:
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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:
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Date:
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09-Apr-08
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Release date:
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27-May-08
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PROCHECK
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Headers
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References
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P11473
(VDR_HUMAN) -
Vitamin D3 receptor from Homo sapiens
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Seq:
Struc:
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427 a.a.
254 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Chem Biol
15:383-392
(2008)
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PubMed id:
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Structure-based design of a superagonist ligand for the vitamin D nuclear receptor.
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S.Hourai,
L.C.Rodrigues,
P.Antony,
B.Reina-San-Martin,
F.Ciesielski,
B.C.Magnier,
K.Schoonjans,
A.Mouriño,
N.Rochel,
D.Moras.
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ABSTRACT
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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.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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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.
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J Mol Biol,
396,
441-451.
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PDB codes:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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Links
