PDBsum entry 2hcd

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protein ligands links
Gene regulation PDB id
Protein chain
239 a.a. *
Waters ×38
* Residue conservation analysis
PDB id:
Name: Gene regulation
Title: Crystal structure of the ligand binding domain of the vitamin d nuclear receptor in complex with gemini and a coactivator peptide
Structure: Vitamin d receptor. Chain: a. Fragment: ligand binding domain. Engineered: yes. Src-1 from nuclear receptor coactivator 1. Chain: b. Synonym: ncoa-1, steroid receptor coactivator 1, src-1, rip160, protein hin-2, ny-ren-52 antigen. Engineered: yes
Source: Danio rerio. Zebrafish. Organism_taxid: 7955. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes. Other_details: this sequence occurs naturally in humans.
2.60Å     R-factor:   0.204     R-free:   0.260
Authors: F.Ciesielski,N.Rochel,D.Moras
Key ref: F.Ciesielski et al. (2007). Adaptability of the Vitamin D nuclear receptor to the synthetic ligand Gemini: remodelling the LBP with one side chain rotation. J Steroid Biochem Mol Biol, 103, 235-242. PubMed id: 17218092 DOI: 10.1016/j.jsbmb.2006.12.003
16-Jun-06     Release date:   01-May-07    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9PTN2  (VDRA_DANRE) -  Vitamin D3 receptor A
453 a.a.
239 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 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.jsbmb.2006.12.003 J Steroid Biochem Mol Biol 103:235-242 (2007)
PubMed id: 17218092  
Adaptability of the Vitamin D nuclear receptor to the synthetic ligand Gemini: remodelling the LBP with one side chain rotation.
F.Ciesielski, N.Rochel, D.Moras.
The crystal structure of the ligand binding domain (LBD) of the wild-type Vitamin D receptor (VDR) of zebrafish bound to Gemini, a synthetic agonist ligand with two identical side chains branching at carbon 20 reveals a ligand-dependent structural rearrangement of the ligand binding pocket (LBP). The rotation of a Leu side chain opens the access to a channel that can accommodate the second side chain of the ligand. The 25% increase of the LBP's volume does not alter the essential agonist features of VDR. The possibility to adapt the LBP to novel ligands with different chemistry and/or structure opens new perspectives in the design of more specifically targeted ligands.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21291553 M.D.Krasowski, N.Ai, L.R.Hagey, E.M.Kollitz, S.W.Kullman, E.J.Reschly, and S.Ekins (2011).
The evolution of farnesoid X, vitamin D, and pregnane X receptors: insights from the green-spotted pufferfish (Tetraodon nigriviridis) and other non-mammalian species.
  BMC Biochem, 12, 5.  
19183053 A.Teichert, L.A.Arnold, S.Otieno, Y.Oda, I.Augustinaite, T.R.Geistlinger, R.W.Kriwacki, R.K.Guy, and D.D.Bikle (2009).
Quantification of the vitamin D receptor-coregulator interaction.
  Biochemistry, 48, 1454-1461.  
19685888 H.Maehr, H.J.Lee, B.Perry, N.Suh, and M.R.Uskokovic (2009).
Calcitriol derivatives with two different side chains at C-20. V. Potent inhibitors of mammary carcinogenesis and inducers of leukemia differentiation.
  J Med Chem, 52, 5505-5519.  
19251824 Y.S.Lin, K.Yasuda, M.Assem, C.Cline, J.Barber, C.W.Li, V.Kholodovych, N.Ai, J.D.Chen, W.J.Welsh, S.Ekins, and E.G.Schuetz (2009).
The major human pregnane X receptor (PXR) splice variant, PXR.2, exhibits significantly diminished ligand-activated transcriptional regulation.
  Drug Metab Dispos, 37, 1295-1304.  
18940664 G.Eelen, N.Valle, Y.Sato, N.Rochel, L.Verlinden, P.De Clercq, D.Moras, R.Bouillon, A.Muñoz, and A.Verstuyf (2008).
Superagonistic fluorinated vitamin D3 analogs stabilize helix 12 of the vitamin D receptor.
  Chem Biol, 15, 1029-1034.
PDB code: 3dr1
19138995 H.J.Lee, S.Paul, N.Atalla, P.E.Thomas, X.Lin, I.Yang, B.Buckley, G.Lu, X.Zheng, Y.R.Lou, A.H.Conney, H.Maehr, L.Adorini, M.Uskokovic, and N.Suh (2008).
Gemini vitamin D analogues inhibit estrogen receptor-positive and estrogen receptor-negative mammary tumorigenesis without hypercalcemic toxicity.
  Cancer Prev Res (Phila), 1, 476-484.  
18651760 M.D.Krasowski, E.J.Reschly, and S.Ekins (2008).
Intrinsic disorder in nuclear hormone receptors.
  J Proteome Res, 7, 4359-4372.  
18384689 S.Ekins, E.J.Reschly, L.R.Hagey, and M.D.Krasowski (2008).
Evolution of pharmacologic specificity in the pregnane X receptor.
  BMC Evol Biol, 8, 103.  
18410235 T.A.Craig, S.Sommer, C.R.Sussman, J.P.Grande, and R.Kumar (2008).
Expression and regulation of the vitamin D receptor in the zebrafish, Danio rerio.
  J Bone Miner Res, 23, 1486-1496.  
17997857 E.J.Reschly, A.C.Bainy, J.J.Mattos, L.R.Hagey, N.Bahary, S.R.Mada, J.Ou, R.Venkataramanan, and M.D.Krasowski (2007).
Functional evolution of the vitamin D and pregnane X receptors.
  BMC Evol Biol, 7, 222.  
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