PDBsum entry 1rkh

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Hormone/growth factor receptor PDB id
Protein chains
242 a.a. *
11 a.a. *
Waters ×68
* Residue conservation analysis
PDB id:
Name: Hormone/growth factor receptor
Title: Crystal structure of the rat vitamin d receptor ligand binding domain complexed with 2am20r and a synthetic peptide containing the nr2 box of drip 205
Structure: Vitamin d3 receptor. Chain: a. Fragment: ligand binding domain. Synonym: vdr, 1,25-dihydroxyvitamin d3 receptor. Engineered: yes. Mutation: yes. Peroxisome proliferator-activated receptor binding protein. Chain: c.
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: vdr, nr1i1. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes
Biol. unit: Tetramer (from PQS)
2.28Å     R-factor:   0.182     R-free:   0.218
Authors: J.L.Vanhooke,M.M.Benning,C.B.Bauer,J.W.Pike,H.F Deluca
Key ref:
J.L.Vanhooke et al. (2004). Molecular structure of the rat vitamin D receptor ligand binding domain complexed with 2-carbon-substituted vitamin D3 hormone analogues and a LXXLL-containing coactivator peptide. Biochemistry, 43, 4101-4110. PubMed id: 15065852 DOI: 10.1021/bi036056y
21-Nov-03     Release date:   13-Apr-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P13053  (VDR_RAT) -  Vitamin D3 receptor
423 a.a.
242 a.a.
Protein chain
Pfam   ArchSchema ?
Q15648  (MED1_HUMAN) -  Mediator of RNA polymerase II transcription subunit 1
1581 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/bi036056y Biochemistry 43:4101-4110 (2004)
PubMed id: 15065852  
Molecular structure of the rat vitamin D receptor ligand binding domain complexed with 2-carbon-substituted vitamin D3 hormone analogues and a LXXLL-containing coactivator peptide.
J.L.Vanhooke, M.M.Benning, C.B.Bauer, J.W.Pike, H.F.DeLuca.
We have determined the crystal structures of the ligand binding domain (LBD) of the rat vitamin D receptor in ternary complexes with a synthetic LXXLL-containing peptide and the following four ligands: 1alpha,25-dihydroxyvitamin D(3); 2-methylene-19-nor-(20S)-1alpha,25-dihydroxyvitamin D(3) (2MD); 1alpha-hydroxy-2-methylene-19-nor-(20S)-bishomopregnacalciferol (2MbisP), and 2alpha-methyl-19-nor-1alpha,25-dihydroxyvitamin D(3) (2AM20R). The conformation of the LBD is identical in each complex. Binding of the 2-carbon-modified analogues does not change the positions of the amino acids in the ligand binding site and has no effect on the interactions in the coactivator binding pocket. The CD ring of the superpotent analogue, 2MD, is tilted within the binding site relative to the other ligands in this study and to (20S)-1alpha,25-dihydroxyvitamin D(3) [Tocchini-Valentini et al. (2001) Proc. Natl. Acad. Sci. U.S.A. 98, 5491-5496]. The aliphatic side chain of 2MD follows a different path within the binding site; nevertheless, the 25-hydroxyl group at the end of the chain occupies the same position as that of the natural ligand, and the hydrogen bonds with histidines 301 and 393 are maintained. 2MbisP binds to the receptor despite the absence of the 25-hydroxyl group. A water molecule is observed between His 301 and His 393 in this structure, and it preserves the orientation of the histidines in the binding site. Although the alpha-chair conformer is highly favored in solution for the A ring of 2AM20R, the crystal structures demonstrate that this ring assumes the beta-chair conformation in all cases, and the 1alpha-hydroxyl group is equatorial. The peptide folds as a helix and is anchored through hydrogen bonds to a surface groove formed by helices 3, 4, and 12. Electrostatic and hydrophobic interactions between the peptide and the LBD stabilize the active receptor conformation. This stablization appears necessary for crystal growth.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21458526 J.Cui, C.Ma, J.Qiu, X.Ma, X.Wang, H.Chen, and B.Huang (2011).
A novel interaction between insulin-like growth factor binding protein-6 and the vitamin D receptor inhibits the role of vitamin D3 in osteoblast differentiation.
  Mol Cell Endocrinol, 338, 84-92.  
21119732 L.A.Plum, and H.F.DeLuca (2010).
Vitamin D, disease and therapeutic opportunities.
  Nat Rev Drug Discov, 9, 941-955.  
20535127 N.J.Nieves, J.M.Ahrens, L.A.Plum, H.F.DeLuca, and M.Clagett-Dame (2010).
Identification of a unique subset of 2-methylene-19-nor analogs of vitamin D with comedolytic activity in the rhino mouse.
  J Invest Dermatol, 130, 2359-2367.  
20693691 S.Kakuda, S.Ishizuka, H.Eguchi, M.T.Mizwicki, A.W.Norman, and M.Takimoto-Kamimura (2010).
Structural basis of the histidine-mediated vitamin D receptor agonistic and antagonistic mechanisms of (23S)-25-dehydro-1alpha-hydroxyvitamin D3-26,23-lactone.
  Acta Crystallogr D Biol Crystallogr, 66, 918-926.
PDB codes: 3a2h 3a2i 3a2j
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.  
18432454 A.K.Ormerod, Z.Xing, N.G.Pedigo, A.Mishra, and D.M.Kaetzel (2008).
The calcitriol analogue EB1089 impairs alveolarization and induces localized regions of increased fibroblast density in neonatal rat lung.
  Exp Lung Res, 34, 155-182.  
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
18844850 H.F.DeLuca (2008).
Evolution of our understanding of vitamin D.
  Nutr Rev, 66, S73-S87.  
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.  
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.  
  18997319 S.Kakuda, K.Okada, H.Eguchi, K.Takenouchi, W.Hakamata, M.Kurihara, and M.Takimoto-Kamimura (2008).
Structure of the ligand-binding domain of rat VDR in complex with the nonsecosteroidal vitamin D3 analogue YR301.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 970-973.
PDB code: 2zfx
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.  
17223545 J.W.Pike, M.B.Meyer, M.Watanuki, S.Kim, L.A.Zella, J.A.Fretz, M.Yamazaki, and N.K.Shevde (2007).
Perspectives on mechanisms of gene regulation by 1,25-dihydroxyvitamin D3 and its receptor.
  J Steroid Biochem Mol Biol, 103, 389-395.  
17254542 L.A.Zella, C.Y.Chang, D.P.McDonnell, and J.Wesley Pike (2007).
The vitamin D receptor interacts preferentially with DRIP205-like LxxLL motifs.
  Arch Biochem Biophys, 460, 206-212.  
16724925 E.J.Reschly, and M.D.Krasowski (2006).
Evolution and function of the NR1I nuclear hormone receptor subfamily (VDR, PXR, and CAR) with respect to metabolism of xenobiotics and endogenous compounds.
  Curr Drug Metab, 7, 349-365.  
16478719 F.Molnár, M.Peräkylä, and C.Carlberg (2006).
Vitamin D receptor agonists specifically modulate the volume of the ligand-binding pocket.
  J Biol Chem, 281, 10516-10526.  
16491322 L.A.Plum, L.A.Fitzpatrick, X.Ma, N.C.Binkley, J.B.Zella, M.Clagett-Dame, and H.F.DeLuca (2006).
2MD, a new anabolic agent for osteoporosis treatment.
  Osteoporos Int, 17, 704-715.  
16936639 R.Sánchez-Martínez, A.I.Castillo, A.Steinmeyer, and A.Aranda (2006).
The retinoid X receptor ligand restores defective signalling by the vitamin D receptor.
  EMBO Rep, 7, 1030-1034.  
16543149 S.Shah, M.N.Islam, S.Dakshanamurthy, I.Rizvi, M.Rao, R.Herrell, G.Zinser, M.Valrance, A.Aranda, D.Moras, A.Norman, J.Welsh, and S.W.Byers (2006).
The molecular basis of vitamin D receptor and beta-catenin crossregulation.
  Mol Cell, 21, 799-809.  
16160732 H.Z.Ke, H.Qi, D.T.Crawford, H.A.Simmons, G.Xu, M.Li, L.Plum, M.Clagett-Dame, H.F.DeLuca, D.D.Thompson, and T.A.Brown (2005).
A new vitamin D analog, 2MD, restores trabecular and cortical bone mass and strength in ovariectomized rats with established osteopenia.
  J Bone Miner Res, 20, 1742-1755.  
16197547 M.D.Krasowski, K.Yasuda, L.R.Hagey, and E.G.Schuetz (2005).
Evolutionary selection across the nuclear hormone receptor superfamily with a focus on the NR1I subfamily (vitamin D, pregnane X, and constitutive androstane receptors).
  Nucl Recept, 3, 2.  
15578590 P.W.Jurutka, P.D.Thompson, G.K.Whitfield, K.R.Eichhorst, N.Hall, C.E.Dominguez, J.C.Hsieh, C.A.Haussler, and M.R.Haussler (2005).
Molecular and functional comparison of 1,25-dihydroxyvitamin D(3) and the novel vitamin D receptor ligand, lithocholic acid, in activating transcription of cytochrome P450 3A4.
  J Cell Biochem, 94, 917-943.  
16130132 W.Sicinska, W.M.Westler, and H.F.DeLuca (2005).
NMR assignments of tryptophan residue in apo and holo LBD-rVDR.
  Proteins, 61, 461-467.  
16301798 Z.Q.Fu (2005).
Three-dimensional model-free experimental error correction of protein crystal diffraction data with free-R test.
  Acta Crystallogr D Biol Crystallogr, 61, 1643-1648.  
15118084 L.A.Plum, J.M.Prahl, X.Ma, R.R.Sicinski, S.Gowlugari, M.Clagett-Dame, and H.F.DeLuca (2004).
Biologically active noncalcemic analogs of 1alpha,25-dihydroxyvitamin D with an abbreviated side chain containing no hydroxyl.
  Proc Natl Acad Sci U S A, 101, 6900-6904.  
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.