PDBsum entry 2hb7

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protein ligands links
Gene regulation PDB id
Protein chain
254 a.a. *
Waters ×170
* Residue conservation analysis
PDB id:
Name: Gene regulation
Title: Crystal structure of vdr lbd in complex with 2alpha(3- hydroxy-1-propyl) calcitriol
Structure: Vitamin d3 receptor. Chain: a. Fragment: ligand binding domain. Synonym: vitamin d nuclear receptor, vdr, 1,25- dihydroxyvitamin d3 receptor. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
1.80Å     R-factor:   0.187     R-free:   0.204
Authors: S.Hourai,N.Rochel,D.Moras
Key ref: S.Hourai et al. (2006). Probing a water channel near the A-ring of receptor-bound 1 alpha,25-dihydroxyvitamin D3 with selected 2 alpha-substituted analogues. J Med Chem, 49, 5199-5205. PubMed id: 16913708 DOI: 10.1021/jm0604070
14-Jun-06     Release date:   29-Aug-06    
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Protein chain
Pfam   ArchSchema ?
P11473  (VDR_HUMAN) -  Vitamin D3 receptor
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: 10.1021/jm0604070 J Med Chem 49:5199-5205 (2006)
PubMed id: 16913708  
Probing a water channel near the A-ring of receptor-bound 1 alpha,25-dihydroxyvitamin D3 with selected 2 alpha-substituted analogues.
S.Hourai, T.Fujishima, A.Kittaka, Y.Suhara, H.Takayama, N.Rochel, D.Moras.
The crystal structure of the vitamin D receptor (VDR) in complex with 1 alpha,25(OH)2D3 revealed the presence of several water molecules near the A-ring linking the ligand C-2 position to the protein surface. Here, we report the crystal structures of the human VDR ligand binding domain bound to selected C-2 alpha substituted analogues, namely, methyl, propyl, propoxy, hydroxypropyl, and hydroxypropoxy. These specific replacements do not modify the structure of the protein or the ligand, but with the exception of the methyl substituent, all analogues affect the presence and/or the location of the above water molecules. The integrity of the channel interactions and specific C-2 alpha analogue directed additional interactions correlate with the binding affinity of the ligands. In contrast, the resulting loss or gain of H-bonds does not reflect the magnitude of HL60 cell differentiation. Our overall findings highlight a rational approach to the design of more potent ligands by building in features revealed in the crystal structures.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21472188 H.Saitoh, T.Chida, K.Takagi, K.Horie, Y.Sawai, Y.Nakamura, Y.Harada, K.Takenouchi, and A.Kittaka (2011).
Synthesis of C-2 substituted vitamin D derivatives having ringed side chains and their biological evaluation, especially biological effect on bone by modification at the C-2 position.
  Org Biomol Chem, 9, 3954-3964.  
19926848 L.Martínez, A.S.Nascimento, F.M.Nunes, K.Phillips, R.Aparicio, S.M.Dias, A.C.Figueira, J.H.Lin, P.Nguyen, J.W.Apriletti, F.A.Neves, J.D.Baxter, P.Webb, M.S.Skaf, and I.Polikarpov (2009).
Gaining ligand selectivity in thyroid hormone receptors via entropy.
  Proc Natl Acad Sci U S A, 106, 20717-20722.
PDB codes: 3jzb 3jzc
18836710 M.Peräkylä (2009).
Ligand unbinding pathways from the vitamin D receptor studied by molecular dynamics simulations.
  Eur Biophys J, 38, 185-198.  
17904370 N.Yoshimoto, Y.Inaba, S.Yamada, M.Makishima, M.Shimizu, and K.Yamamoto (2008).
2-Methylene 19-nor-25-dehydro-1alpha-hydroxyvitamin D3 26,23-lactones: synthesis, biological activities and molecular basis of passive antagonism.
  Bioorg Med Chem, 16, 457-473.  
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