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PDBsum entry 2zxn

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protein ligands Protein-protein interface(s) links
Transcription PDB id
2zxn
Jmol
Contents
Protein chains
240 a.a. *
11 a.a. *
Ligands
JC1
Waters ×50
* Residue conservation analysis
PDB id:
2zxn
Name: Transcription
Title: A new class of vitamin d receptor ligands that induce structural rearrangement of the ligand-binding pocket
Structure: Vitamin d3 receptor. Chain: a. Fragment: ligand binding domain, unp residues 116-423. Synonym: vdr, 1,25-dihydroxyvitamin d3 receptor, nuclear receptor subfamily 1 group i member 1. Engineered: yes. Mediator of RNA polymerase ii transcription subunit 1. Chain: c.
Source: Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: nr1i1, vdr. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: synthetic peptide
Resolution:
2.10Å     R-factor:   0.209     R-free:   0.251
Authors: M.Nakabayashi,T.Ikura,N.Ito
Key ref: Y.Inaba et al. (2009). A new class of vitamin D analogues that induce structural rearrangement of the ligand-binding pocket of the receptor. J Med Chem, 52, 1438-1449. PubMed id: 19193059 DOI: 10.1021/jm8014348
Date:
04-Jan-09     Release date:   17-Feb-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P13053  (VDR_RAT) -  Vitamin D3 receptor
Seq:
Struc:
423 a.a.
240 a.a.
Protein chain
Pfam   ArchSchema ?
A1L0Z0  (MED1_XENTR) -  Mediator of RNA polymerase II transcription subunit 1
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1573 a.a.
11 a.a.
Key:    PfamA domain  PfamB 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: 10.1021/jm8014348 J Med Chem 52:1438-1449 (2009)
PubMed id: 19193059  
 
 
A new class of vitamin D analogues that induce structural rearrangement of the ligand-binding pocket of the receptor.
Y.Inaba, N.Yoshimoto, Y.Sakamaki, M.Nakabayashi, T.Ikura, H.Tamamura, N.Ito, M.Shimizu, K.Yamamoto.
 
  ABSTRACT  
 
To identify novel vitamin D receptor (VDR) ligands that induce a novel architecture within the ligand-binding pocket (LBP), we have investigated eight 22-butyl-1alpha,24-dihydroxyvitamin D(3) derivatives (3-10), all having a butyl group as the branched alkyl side chain. We found that the 22S-butyl-20-epi-25,26,27-trinorvitamin D derivative 5 was a potent VDR agonist, whereas the corresponding compound 4 with the natural configuration at C(20) was a potent VDR antagonist. Analogues with the full vitamin D(3) side chain were less potent agonist, and whether they were agonists or antagonists depended on the 24-configuration. X-ray crystal structures demonstrated that the VDR-LBD accommodating the potent agonist 5 has an architecture wherein the lower side and the helix 11 side of the LBP is simply expanded relative to the canonical active-VDR situation; in contrast, the potent antagonist 4 induces an extra cavity to accommodate the branched moiety. This is the first report of a VDR antagonist that generates a new cavity to alter the canonical pocket structure of the ligand occupied VDR.