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PDBsum entry 1db1

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protein ligands links
Gene regulation PDB id
1db1
Jmol PyMol
Contents
Protein chain
250 a.a. *
Ligands
VDX
Waters ×164
* Residue conservation analysis
PDB id:
1db1
Name: Gene regulation
Title: Crystal structure of the nuclear receptor for vitamin d complexed to vitamin d
Structure: Vitamin d nuclear receptor. Chain: a. Fragment: ligand binding domain. Synonym: vdr. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.80Å     R-factor:   0.191     R-free:   0.214
Authors: N.Rochel,J.M.Wurtz,A.Mitschler,B.Klaholz,D.Moras
Key ref:
N.Rochel et al. (2000). The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand. Mol Cell, 5, 173-179. PubMed id: 10678179 DOI: 10.1016/S1097-2765(00)80413-X
Date:
02-Nov-99     Release date:   31-Jan-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P11473  (VDR_HUMAN) -  Vitamin D3 receptor
Seq:
Struc:
427 a.a.
250 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     3 terms  

 

 
DOI no: 10.1016/S1097-2765(00)80413-X Mol Cell 5:173-179 (2000)
PubMed id: 10678179  
 
 
The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand.
N.Rochel, J.M.Wurtz, A.Mitschler, B.Klaholz, D.Moras.
 
  ABSTRACT  
 
The action of 1 alpha, 25-dihydroxyvitamin D3 is mediated by its nuclear receptor (VDR), a ligand-dependent transcription regulator. We report the 1.8 A resolution crystal structure of the complex between a VDR ligand-binding domain (LBD) construct lacking the highly variable VDR-specific insertion domain and vitamin D. The construct exhibits the same binding affinity for vitamin D and transactivation ability as the wild-type protein, showing that the N-terminal part of the LBD is essential for its structural and functional integrity while the large insertion peptide is dispensable. The structure reveals the active conformation of the bound ligand and allows understanding of the different binding properties of some synthetic analogs.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Vitamin D Bound to Its Cognate Nuclear Receptor(a–d) Chemical structure of 1,25(OH)[2]D[3] and analogs. (a) 1,25(OH)[2]D[3]: 1α,25-dihydroxyvitamin D[3]; (c) MC903: 1α,24S-dihydroxy-22-ene-25,26,27-cyclopropylvitamin D[3]; (d) EB1089: 1α,25-dihydroxy-22,24diene-24,26,27-trihomovitamin D[3]; (b) KH1060: 1α,25-dihydroxy-20-epi-22-oxa-24,26,27-trihomovitamin D[3].(e) Overall fold of the hVDR ligand-binding domain. The helices are represented as cylinders and β sheets as arrows. The whole structure is colored in gray except the helix H12, shown as a purple cylinder. The ligand is depicted in yellow. The insertion domain location is shown in green. The reconnected residues are indicated, together with their sequence numbering.
Figure 3.
Figure 3. Close-up Views of Selected Regions of the hVDR-LBD Crystal Structure(a and b) Comparison of the β sheet region of RARγ (a) and VDR (b) in the same orientation. The RAR and VDR are colored in pink and gray, respectively. Their ligands, retinoic acid and 1,25(OH)[2]D[3], are colored in yellow.(c) Intramolecular interactions of helix H12 in VDR. The side chains of residue involved in polar stabilization of H12 in its agonist position are shown together with the hydrogen bonds (green dots). The backbone of the protein is colored in gray except for helix H12 in purple. The side chain atoms are colored in gray for carbon, red for oxygen atoms, and blue for nitrogen. The ligand is colored in yellow with the hydroxyl groups shown as red spheres.(d) Stereo view of 1,25(OH[2])D[3] in the hVDR ligand-binding pocket. The ligand molecule is shown in the experimental electron density omit map contoured at 1.0 standard deviation. The hydroxyl moieties are depicted as red spheres. Water molecules surrounding the A ring are shown as purple spheres. Hydrogen bonds are shown as green dotted lines. In both pictures, the carbon atoms are colored in gray, and oxygen and nitrogen atoms are colored in red and blue, respectively.
 
  The above figures are reprinted by permission from Cell Press: Mol Cell (2000, 5, 173-179) copyright 2000.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21287548 C.G.Mayne, J.A.Spanier, L.M.Relland, C.B.Williams, and C.E.Hayes (2011).
1,25-Dihydroxyvitamin D(3) acts directly on the T lymphocyte vitamin D receptor to inhibit experimental autoimmune encephalomyelitis.
  Eur J Immunol, 41, 822-832.  
21478866 J.Zhang, M.J.Chalmers, K.R.Stayrook, L.L.Burris, Y.Wang, S.A.Busby, B.D.Pascal, R.D.Garcia-Ordonez, J.B.Bruning, M.A.Istrate, D.J.Kojetin, J.A.Dodge, T.P.Burris, and P.R.Griffin (2011).
DNA binding alters coactivator interaction surfaces of the intact VDR-RXR complex.
  Nat Struct Mol Biol, 18, 556-563.  
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.  
21478865 N.Rochel, F.Ciesielski, J.Godet, E.Moman, M.Roessle, C.Peluso-Iltis, M.Moulin, M.Haertlein, P.Callow, Y.Mély, D.I.Svergun, and D.Moras (2011).
Common architecture of nuclear receptor heterodimers on DNA direct repeat elements with different spacings.
  Nat Struct Mol Biol, 18, 564-570.  
21305095 V.Sikervar, and P.L.Fuchs (2011).
S(N)2' addition/1,2-elimination of dimethylsulfonium methylide with epoxy vinyl sulfones: synthesis of exocyclic cross-conjugated dienyl sulfones.
  Chem Commun (Camb), 47, 3472-3474.  
20360850 A.T.Slominski, Z.Janjetovic, B.E.Fuller, M.A.Zmijewski, R.C.Tuckey, M.N.Nguyen, T.Sweatman, W.Li, J.Zjawiony, D.Miller, T.C.Chen, G.Lozanski, and M.F.Holick (2010).
Products of vitamin D3 or 7-dehydrocholesterol metabolism by cytochrome P450scc show anti-leukemia effects, having low or absent calcemic activity.
  PLoS One, 5, e9907.  
19737544 F.C.Campbell, H.Xu, M.El-Tanani, P.Crowe, and V.Bingham (2010).
The yin and yang of vitamin D receptor (VDR) signaling in neoplastic progression: operational networks and tissue-specific growth control.
  Biochem Pharmacol, 79, 1-9.  
20723571 L.Jin, and Y.Li (2010).
Structural and functional insights into nuclear receptor signaling.
  Adv Drug Deliv Rev, 62, 1218-1226.  
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.  
20039353 P.Gogoi, R.Sigüeiro, S.Eduardo, and A.Mouriño (2010).
An expeditious route to 1alpha,25-dihydroxyvitamin D(3) and its analogues by an aqueous tandem palladium-catalyzed a-ring closure and suzuki coupling to the C/D unit.
  Chemistry, 16, 1432-1435.  
20148675 P.Huang, V.Chandra, and F.Rastinejad (2010).
Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics.
  Annu Rev Physiol, 72, 247-272.  
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
20236534 S.Marcellini, C.Bruna, J.P.Henríquez, M.Albistur, A.E.Reyes, E.H.Barriga, B.Henríquez, and M.Montecino (2010).
Evolution of the interaction between Runx2 and VDR, two transcription factors involved in osteoblastogenesis.
  BMC Evol Biol, 10, 78.  
19948723 T.T.Wang, B.Dabbas, D.Laperriere, A.J.Bitton, H.Soualhine, L.E.Tavera-Mendoza, S.Dionne, M.J.Servant, A.Bitton, E.G.Seidman, S.Mader, M.A.Behr, and J.H.White (2010).
Direct and indirect induction by 1,25-dihydroxyvitamin D3 of the NOD2/CARD15-defensin beta2 innate immune pathway defective in Crohn disease.
  J Biol Chem, 285, 2227-2231.  
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.  
19427329 A.di Masi, E.De Marinis, P.Ascenzi, and M.Marino (2009).
Nuclear receptors CAR and PXR: Molecular, functional, and biomedical aspects.
  Mol Aspects Med, 30, 297-343.  
19721807 G.N.Brooke, and C.L.Bevan (2009).
The role of androgen receptor mutations in prostate cancer progression.
  Curr Genomics, 10, 18-25.  
19184984 H.Xu, M.McCann, Z.Zhang, G.H.Posner, V.Bingham, M.El-Tanani, and F.C.Campbell (2009).
Vitamin D receptor modulates the neoplastic phenotype through antagonistic growth regulatory signals.
  Mol Carcinog, 48, 758-772.  
19924301 M.E.Beildeck, M.Islam, S.Shah, J.Welsh, and S.W.Byers (2009).
Control of TCF-4 expression by VDR and vitamin D in the mouse mammary gland and colorectal cancer cell lines.
  PLoS One, 4, e7872.  
18836710 M.Peräkylä (2009).
Ligand unbinding pathways from the vitamin D receptor studied by molecular dynamics simulations.
  Eur Biophys J, 38, 185-198.  
19801650 M.T.Mizwicki, C.M.Bula, P.Mahinthichaichan, H.L.Henry, S.Ishizuka, and A.W.Norman (2009).
On the mechanism underlying (23S)-25-dehydro-1alpha(OH)-vitamin D3-26,23-lactone antagonism of hVDRwt gene activation and its switch to a superagonist.
  J Biol Chem, 284, 36292-36301.  
19523546 N.S.Ma, P.J.Malloy, P.Pitukcheewanont, D.Dreimane, M.E.Geffner, and D.Feldman (2009).
Hereditary vitamin D resistant rickets: identification of a novel splice site mutation in the vitamin D receptor gene and successful treatment with oral calcium therapy.
  Bone, 45, 743-746.  
19241402 S.A.Birlea, G.E.Costin, and D.A.Norris (2009).
New insights on therapy with vitamin D analogs targeting the intracellular pathways that control repigmentation in human vitiligo.
  Med Res Rev, 29, 514-546.  
19223058 T.Kaya, N.Swamy, K.S.Persons, S.Ray, S.C.Mohr, and R.Ray (2009).
Covalent labeling of nuclear vitamin D receptor with affinity labeling reagents containing a cross-linking probe at three different positions of the parent ligand: structural and biochemical implications.
  Bioorg Chem, 37, 57-63.  
19049339 Y.Zhou, J.Wang, P.J.Malloy, Z.Dolezel, and D.Feldman (2009).
Compound heterozygous mutations in the vitamin D receptor in a patient with hereditary 1,25-dihydroxyvitamin D-resistant rickets with alopecia.
  J Bone Miner Res, 24, 643-651.  
18362391 E.J.Reschly, N.Ai, S.Ekins, W.J.Welsh, L.R.Hagey, A.F.Hofmann, and M.D.Krasowski (2008).
Evolution of the bile salt nuclear receptor FXR in vertebrates.
  J Lipid Res, 49, 1577-1587.  
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.  
18505808 J.H.White (2008).
Vitamin D signaling, infectious diseases, and regulation of innate immunity.
  Infect Immun, 76, 3837-3843.  
18550844 L.E.Tavera-Mendoza, T.D.Quach, B.Dabbas, J.Hudon, X.Liao, A.Palijan, J.L.Gleason, and J.H.White (2008).
Incorporation of histone deacetylase inhibition into the structure of a nuclear receptor agonist.
  Proc Natl Acad Sci U S A, 105, 8250-8255.  
18651760 M.D.Krasowski, E.J.Reschly, and S.Ekins (2008).
Intrinsic disorder in nuclear hormone receptors.
  J Proteome Res, 7, 4359-4372.  
18844852 M.R.Haussler, C.A.Haussler, L.Bartik, G.K.Whitfield, J.C.Hsieh, S.Slater, and P.W.Jurutka (2008).
Vitamin D receptor: molecular signaling and actions of nutritional ligands in disease prevention.
  Nutr Rev, 66, S98-112.  
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.  
18214952 R.Minai, Y.Matsuo, H.Onuki, and H.Hirota (2008).
Method for comparing the structures of protein ligand-binding sites and application for predicting protein-drug interactions.
  Proteins, 72, 367-381.  
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.  
17368178 C.M.Bula, J.E.Bishop, and A.W.Norman (2007).
Conservative mutageneic perturbations of amino acids connecting helix 12 in the 1alpha,25(OH)2-D3 receptor (VDR) to the ligand cause significant transactivational effects.
  J Steroid Biochem Mol Biol, 103, 286-292.  
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.  
17368177 M.T.Mizwicki, C.M.Bula, J.E.Bishop, and A.W.Norman (2007).
New insights into Vitamin D sterol-VDR proteolysis, allostery, structure-function from the perspective of a conformational ensemble model.
  J Steroid Biochem Mol Biol, 103, 243-262.  
17078924 P.J.Malloy, J.Wang, L.Peng, S.Nayak, J.M.Sisk, C.C.Thompson, and D.Feldman (2007).
A unique insertion/duplication in the VDR gene that truncates the VDR causing hereditary 1,25-dihydroxyvitamin D-resistant rickets without alopecia.
  Arch Biochem Biophys, 460, 285-292.  
17565270 S.Kato, M.S.Kim, K.Yamaoka, and R.Fujiki (2007).
Mechanisms of transcriptional repression by 1,25(OH)2 vitamin D.
  Curr Opin Nephrol Hypertens, 16, 297-304.  
17310066 T.I.Ellison, R.L.Eckert, and P.N.MacDonald (2007).
Evidence for 1,25-dihydroxyvitamin D3-independent transactivation by the vitamin D receptor: uncoupling the receptor and ligand in keratinocytes.
  J Biol Chem, 282, 10953-10962.  
16819881 A.Q.Hassan, and J.T.Koh (2006).
A functionally orthogonal ligand-receptor pair created by targeting the allosteric mechanism of the thyroid hormone receptor.
  J Am Chem Soc, 128, 8868-8874.  
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.  
17077522 E.Takahashi, K.Nakagawa, Y.Suhara, A.Kittaka, K.Nihei, K.Konno, H.Takayama, K.Ozono, and T.Okano (2006).
Biological activities of 2alpha-substituted analogues of 1alpha,25-dihydroxyvitamin D3 in transcriptional regulation and human promyelocytic leukemia (HL-60) cell proliferation and differentiation.
  Biol Pharm Bull, 29, 2246-2250.  
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.  
17064257 G.Jones, D.Jones, P.Teal, A.Sapa, and M.Wozniak (2006).
The retinoid-X receptor ortholog, ultraspiracle, binds with nanomolar affinity to an endogenous morphogenetic ligand.
  FEBS J, 273, 4983-4996.  
16519596 I.Ramasamy (2006).
Recent advances in physiological calcium homeostasis.
  Clin Chem Lab Med, 44, 237-273.  
16863441 M.Iyer, E.J.Reschly, and M.D.Krasowski (2006).
Functional evolution of the pregnane X receptor.
  Expert Opin Drug Metab Toxicol, 2, 381-397.  
16753019 M.Nguyen, A.d'Alesio, J.M.Pascussi, R.Kumar, M.D.Griffin, X.Dong, H.Guillozo, M.Rizk-Rabin, C.Sinding, P.Bougnères, F.Jehan, and M.Garabédian (2006).
Vitamin D-resistant rickets and type 1 diabetes in a child with compound heterozygous mutations of the vitamin D receptor (L263R and R391S): dissociated responses of the CYP-24 and rel-B promoters to 1,25-dihydroxyvitamin D3.
  J Bone Miner Res, 21, 886-894.  
16871612 N.Saito, and A.Kittaka (2006).
Highly potent vitamin D receptor antagonists: design, synthesis, and biological evaluation.
  Chembiochem, 7, 1479-1490.  
16834332 S.M.Noble, V.E.Carnahan, L.B.Moore, T.Luntz, H.Wang, O.R.Ittoop, J.B.Stimmel, P.R.Davis-Searles, R.E.Watkins, G.B.Wisely, E.LeCluyse, A.Tripathy, D.P.McDonnell, and M.R.Redinbo (2006).
Human PXR forms a tryptophan zipper-mediated homodimer.
  Biochemistry, 45, 8579-8589.  
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.  
  16403216 T.G.Marshall, R.E.Lee, and F.E.Marshall (2006).
Common angiotensin receptor blockers may directly modulate the immune system via VDR, PPAR and CCR2b.
  Theor Biol Med Model, 3, 1.  
15616833 B.Windshügel, J.Jyrkkärinne, A.Poso, P.Honkakoski, and W.Sippl (2005).
Molecular dynamics simulations of the human CAR ligand-binding domain: deciphering the molecular basis for constitutive activity.
  J Mol Model, 11, 69-79.  
15971062 C.Mathieu, C.Gysemans, A.Giulietti, and R.Bouillon (2005).
Vitamin D and diabetes.
  Diabetologia, 48, 1247-1257.  
15888456 F.Molnár, M.Matilainen, and C.Carlberg (2005).
Structural determinants of the agonist-independent association of human peroxisome proliferator-activated receptors with coactivators.
  J Biol Chem, 280, 26543-26556.  
15572376 J.Jyrkkärinne, B.Windshügel, J.Mäkinen, M.Ylisirniö, M.Peräkylä, A.Poso, W.Sippl, and P.Honkakoski (2005).
Amino acids important for ligand specificity of the human constitutive androstane receptor.
  J Biol Chem, 280, 5960-5971.  
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.  
15826954 P.Iordanidou, E.Aggelidou, C.Demetriades, and M.Hadzopoulou-Cladaras (2005).
Distinct amino acid residues may be involved in coactivator and ligand interactions in hepatocyte nuclear factor-4alpha.
  J Biol Chem, 280, 21810-21819.  
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.  
16204233 R.Yasmin, R.M.Williams, M.Xu, and N.Noy (2005).
Nuclear import of the retinoid X receptor, the vitamin D receptor, and their mutual heterodimer.
  J Biol Chem, 280, 40152-40160.  
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.  
16059639 Y.Liu, Q.Shen, P.J.Malloy, E.Soliman, X.Peng, S.Kim, J.W.Pike, D.Feldman, and S.Christakos (2005).
Enhanced coactivator binding and transcriptional activation of mutant vitamin D receptors from patients with hereditary 1,25-dihydroxyvitamin D-resistant rickets by phosphorylation and vitamin D analogs.
  J Bone Miner Res, 20, 1680-1691.  
14708019 A.W.Norman, M.T.Mizwicki, and D.P.Norman (2004).
Steroid-hormone rapid actions, membrane receptors and a conformational ensemble model.
  Nat Rev Drug Discov, 3, 27-41.  
15175162 D.J.Taatjes, and R.Tjian (2004).
Structure and function of CRSP/Med2; a promoter-selective transcriptional coactivator complex.
  Mol Cell, 14, 675-683.  
15195149 D.J.Taatjes, T.Schneider-Poetsch, and R.Tjian (2004).
Distinct conformational states of nuclear receptor-bound CRSP-Med complexes.
  Nat Struct Mol Biol, 11, 664-671.  
15246430 G.Benoit, M.Malewicz, and T.Perlmann (2004).
Digging deep into the pockets of orphan nuclear receptors: insights from structural studies.
  Trends Cell Biol, 14, 369-376.  
14982928 K.Duda, Y.I.Chi, and S.E.Shoelson (2004).
Structural basis for HNF-4alpha activation by ligand and coactivator binding.
  J Biol Chem, 279, 23311-23316.
PDB code: 1pzl
15610733 K.Suino, L.Peng, R.Reynolds, Y.Li, J.Y.Cha, J.J.Repa, S.A.Kliewer, and H.E.Xu (2004).
The nuclear xenobiotic receptor CAR: structural determinants of constitutive activation and heterodimerization.
  Mol Cell, 16, 893-905.
PDB code: 1xls
15610734 L.Shan, J.Vincent, J.S.Brunzelle, I.Dussault, M.Lin, I.Ianculescu, M.A.Sherman, B.M.Forman, and E.J.Fernandez (2004).
Structure of the murine constitutive androstane receptor complexed to androstenol: a molecular basis for inverse agonism.
  Mol Cell, 16, 907-917.
PDB code: 1xnx
15324816 M.Peräkylä, F.Molnár, and C.Carlberg (2004).
A structural basis for the species-specific antagonism of 26,23-lactones on vitamin D signaling.
  Chem Biol, 11, 1147-1156.  
15326291 M.T.Mizwicki, D.Keidel, C.M.Bula, J.E.Bishop, L.P.Zanello, J.M.Wurtz, D.Moras, and A.W.Norman (2004).
Identification of an alternative ligand-binding pocket in the nuclear vitamin D receptor and its functional importance in 1alpha,25(OH)2-vitamin D3 signaling.
  Proc Natl Acad Sci U S A, 101, 12876-12881.  
15190891 P.J.Malloy, R.Xu, A.Cattani, L.Reyes, and D.Feldman (2004).
A unique insertion/substitution in helix H1 of the vitamin D receptor ligand binding domain in a patient with hereditary 1,25-dihydroxyvitamin D-resistant rickets.
  J Bone Miner Res, 19, 1018-1024.  
14696037 R.Lin, and J.H.White (2004).
The pleiotropic actions of vitamin D.
  Bioessays, 26, 21-28.  
15610735 R.X.Xu, M.H.Lambert, B.B.Wisely, E.N.Warren, E.E.Weinert, G.M.Waitt, J.D.Williams, J.L.Collins, L.B.Moore, T.M.Willson, and J.T.Moore (2004).
A structural basis for constitutive activity in the human CAR/RXRalpha heterodimer.
  Mol Cell, 16, 919-928.
PDB codes: 1xv9 1xvp
12529333 A.Chauchereau, L.Amazit, M.Quesne, A.Guiochon-Mantel, and E.Milgrom (2003).
Sumoylation of the progesterone receptor and of the steroid receptor coactivator SRC-1.
  J Biol Chem, 278, 12335-12343.  
12612432 A.Kittaka, M.Kurihara, S.Peleg, Y.Suhara, and H.Takayama (2003).
2 alpha-(3-hydroxypropyl)- and 2 alpha-(3-hydroxypropoxy)-1 alpha,25-dihydroxyvitamin D3 accessible to vitamin D receptor mutant related to hereditary vitamin D-resistant rickets.
  Chem Pharm Bull (Tokyo), 51, 357-358.  
14517908 A.Nayeem, S.Krystek, and T.Stouch (2003).
An assessment of protein-ligand binding site polarizability.
  Biopolymers, 70, 201-211.  
12520526 C.Carlberg (2003).
Molecular basis of the selective activity of vitamin D analogues.
  J Cell Biochem, 88, 274-281.  
12796488 H.Yamamoto, N.K.Shevde, A.Warrier, L.A.Plum, H.F.DeLuca, and J.W.Pike (2003).
2-Methylene-19-nor-(20S)-1,25-dihydroxyvitamin D3 potently stimulates gene-specific DNA binding of the vitamin D receptor in osteoblasts.
  J Biol Chem, 278, 31756-31765.  
14595375 I.M.Billas, T.Iwema, J.M.Garnier, A.Mitschler, N.Rochel, and D.Moras (2003).
Structural adaptability in the ligand-binding pocket of the ecdysone hormone receptor.
  Nature, 426, 91-96.
PDB codes: 1r1k 1r20
12529369 J.B.Barry, G.M.Leong, W.B.Church, L.L.Issa, J.A.Eisman, and E.M.Gardiner (2003).
Interactions of SKIP/NCoA-62, TFIIB, and retinoid X receptor with vitamin D receptor helix H10 residues.
  J Biol Chem, 278, 8224-8228.  
12847098 J.C.Hsieh, J.M.Sisk, P.W.Jurutka, C.A.Haussler, S.A.Slater, M.R.Haussler, and C.C.Thompson (2003).
Physical and functional interaction between the vitamin D receptor and hairless corepressor, two proteins required for hair cycling.
  J Biol Chem, 278, 38665-38674.  
12611900 J.M.Maglich, D.J.Parks, L.B.Moore, J.L.Collins, B.Goodwin, A.N.Billin, C.A.Stoltz, S.A.Kliewer, M.H.Lambert, T.M.Willson, and J.T.Moore (2003).
Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes.
  J Biol Chem, 278, 17277-17283.  
12829710 L.Verlinden, A.Verstuyf, C.Verboven, G.Eelen, C.De Ranter, L.J.Gao, Y.J.Chen, I.Murad, M.Choi, K.Yamamoto, S.Yamada, D.Van Haver, M.Vandewalle, P.J.De Clercq, and R.Bouillon (2003).
Previtamin D3 with a trans-fused decalin CD-ring has pronounced genomic activity.
  J Biol Chem, 278, 35476-35482.  
12670540 M.Choi, K.Yamamoto, T.Itoh, M.Makishima, D.J.Mangelsdorf, D.Moras, H.F.DeLuca, and S.Yamada (2003).
Interaction between vitamin D receptor and vitamin D ligands: two-dimensional alanine scanning mutational analysis.
  Chem Biol, 10, 261-270.  
12623229 M.Habeck (2003).
New ligands for defective receptors.
  Drug Discov Today, 8, 236-237.  
12733718 M.T.Mizwicki, and A.W.Norman (2003).
Two key proteins of the vitamin D endocrine system come into crystal clear focus: comparison of the X-ray structures of the nuclear receptor for 1alpha,25(OH)2 vitamin D3, the plasma vitamin D binding protein, and their ligands.
  J Bone Miner Res, 18, 795-806.  
12874825 N.Swamy, K.S.Persons, T.C.Chen, and R.Ray (2003).
1alpha,25-Dihydroxyvitamin D3-3beta-(2)-bromoacetate, an affinity labeling derivative of 1alpha,25-dihydroxyvitamin D3 displays strong antiproliferative and cytotoxic behavior in prostate cancer cells.
  J Cell Biochem, 89, 909-916.  
12577303 S.Christakos, P.Dhawan, Y.Liu, X.Peng, and A.Porta (2003).
New insights into the mechanisms of vitamin D action.
  J Cell Biochem, 88, 695-705.  
12736258 S.Williams, R.K.Bledsoe, J.L.Collins, S.Boggs, M.H.Lambert, A.B.Miller, J.Moore, D.D.McKee, L.Moore, J.Nichols, D.Parks, M.Watson, B.Wisely, and T.M.Willson (2003).
X-ray crystal structure of the liver X receptor beta ligand binding domain: regulation by a histidine-tryptophan switch.
  J Biol Chem, 278, 27138-27143.
PDB code: 1p8d
12424754 S.Yamada, M.Shimizu, and K.Yamamoto (2003).
Structure-function relationships of vitamin D including ligand recognition by the vitamin D receptor.
  Med Res Rev, 23, 89.  
11963993 A.Ohno, M.Shimizu, and S.Yamada (2002).
Fluorinated vitamin D analogs to probe the conformation of vitamin D in its receptor complex: 19F-NMR studies and biological activity.
  Chem Pharm Bull (Tokyo), 50, 475-483.  
11927275 C.Mathieu, and L.Adorini (2002).
The coming of age of 1,25-dihydroxyvitamin D(3) analogs as immunomodulatory agents.
  Trends Mol Med, 8, 174-179.  
11799400 C.Verboven, A.Rabijns, M.De Maeyer, H.Van Baelen, R.Bouillon, and C.De Ranter (2002).
A structural basis for the unique binding features of the human vitamin D-binding protein.
  Nat Struct Biol, 9, 131-136.
PDB codes: 1j78 1j7e
12109997 H.H.Malluche, H.Mawad, and N.J.Koszewski (2002).
Update on vitamin D and its newer analogues: actions and rationale for treatment in chronic renal failure.
  Kidney Int, 62, 367-374.  
11857955 H.Takayama (2002).
[Creation of functional organic compounds and their applications]
  Yakugaku Zasshi, 122, 127-155.  
12101224 I.Dussault, M.Lin, K.Hollister, M.Fan, J.Termini, M.A.Sherman, and B.M.Forman (2002).
A structural model of the constitutive androstane receptor defines novel interactions that mediate ligand-independent activity.
  Mol Cell Biol, 22, 5270-5280.  
12400159 K.Nakagawa (2002).
[Analysis of molecular mechanism of cancer cell differentiation and apoptosis induced by vitamin D3 analogs on the basis of molecular recognition of vitamin D receptor ligand binding domain]
  Yakugaku Zasshi, 122, 781-791.  
12115546 K.Steketee, L.Timmerman, A.C.Ziel-van der Made, P.Doesburg, A.O.Brinkmann, and J.Trapman (2002).
Broadened ligand responsiveness of androgen receptor mutants obtained by random amino acid substitution of H874 and mutation hot spot T877 in prostate cancer.
  Int J Cancer, 100, 309-317.  
12009019 L.L.Issa, G.M.Leong, R.L.Sutherland, and J.A.Eisman (2002).
Vitamin D analogue-specific recruitment of vitamin D receptor coactivators.
  J Bone Miner Res, 17, 879-890.  
11980721 P.L.Shaffer, and D.T.Gewirth (2002).
Structural basis of VDR-DNA interactions on direct repeat response elements.
  EMBO J, 21, 2242-2252.
PDB codes: 1kb2 1kb4 1kb6
12142447 S.H.McLaughlin, and S.E.Jackson (2002).
Folding and stability of the ligand-binding domain of the glucocorticoid receptor.
  Protein Sci, 11, 1926-1936.  
12426368 S.Ozbek, J.Engel, and J.Stetefeld (2002).
Storage function of cartilage oligomeric matrix protein: the crystal structure of the coiled-coil domain in complex with vitamin D(3).
  EMBO J, 21, 5960-5968.
PDB code: 1mz9
12211444 T.M.Nguyen, P.Adiceam, M.L.Kottler, H.Guillozo, M.Rizk-Rabin, F.Brouillard, P.Lagier, C.Palix, J.M.Garnier, and M.Garabedian (2002).
Tryptophan missense mutation in the ligand-binding domain of the vitamin D receptor causes severe resistance to 1,25-dihydroxyvitamin D.
  J Bone Miner Res, 17, 1728-1737.  
12120277 T.M.Willson, and S.A.Kliewer (2002).
PXR, CAR and drug metabolism.
  Nat Rev Drug Discov, 1, 259-266.  
12354121 T.Ostberg, G.Bertilsson, L.Jendeberg, A.Berkenstam, and J.Uppenberg (2002).
Identification of residues in the PXR ligand binding domain critical for species specific and constitutive activation.
  Eur J Biochem, 269, 4896-4904.  
11340063 A.C.Steinmetz, J.P.Renaud, and D.Moras (2001).
Binding of ligands and activation of transcription by nuclear receptors.
  Annu Rev Biophys Biomol Struct, 30, 329-359.  
11689423 C.Stehlin, J.M.Wurtz, A.Steinmetz, E.Greiner, R.Schüle, D.Moras, and J.P.Renaud (2001).
X-ray structure of the orphan nuclear receptor RORbeta ligand-binding domain in the active conformation.
  EMBO J, 20, 5822-5831.
PDB code: 1k4w
11344298 G.Tocchini-Valentini, N.Rochel, J.M.Wurtz, A.Mitschler, and D.Moras (2001).
Crystal structures of the vitamin D receptor complexed to superagonist 20-epi ligands.
  Proc Natl Acad Sci U S A, 98, 5491-5496.
PDB codes: 1ie8 1ie9
11320241 J.S.Sack, K.F.Kish, C.Wang, R.M.Attar, S.E.Kiefer, Y.An, G.Y.Wu, J.E.Scheffler, M.E.Salvati, S.R.Krystek, R.Weinmann, and H.M.Einspahr (2001).
Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone.
  Proc Natl Acad Sci U S A, 98, 4904-4909.
PDB codes: 1i37 1i38
11253921 K.Koyano, Y.Saitoh, J.Oshida, and M.Takimoto-Kamimura (2001).
Dimer and superstructure of the active form of a vitamin D3; 1 alpha,24(R)dihydroxy-vitamin D3 monohydrate, C27O3H44.H2O.
  Chem Pharm Bull (Tokyo), 49, 305-311.  
11400190 K.Mikami, S.Ohba, H.Ohmura, N.Kubodera, K.Nakagawa, and T.Okano (2001).
Asymmetric catalytic ene-cyclization approach to 2-fluoro-19-nor-1,25-dihydroxyvitamin D(3) A-ring analog with significant transactivation activity.
  Chirality, 13, 366-371.  
11253922 M.Shimizu, A.Ohno, and S.Yamada (2001).
(10Z)- and (10E)-19-fluoro-1alpha,25-dihydroxyvitamin D3: an improved synthesis via 19-nor-10-oxo-vitamin D.
  Chem Pharm Bull (Tokyo), 49, 312-317.  
11179963 N.Rochel, G.Tocchini-Valentini, P.F.Egea, K.Juntunen, J.M.Garnier, P.Vihko, and D.Moras (2001).
Functional and structural characterization of the insertion region in the ligand binding domain of the vitamin D nuclear receptor.
  Eur J Biochem, 268, 971-979.  
11455592 P.Rotkiewicz, W.Sicinska, A.Kolinski, and H.F.DeLuca (2001).
Model of three-dimensional structure of vitamin D receptor and its binding mechanism with 1alpha,25-dihydroxyvitamin D(3).
  Proteins, 44, 188-199.  
11271538 S.Gabriëls, D.Van Haver, M.Vandewalle, P.De Clercq, A.Verstuyf, and R.Bouillon (2001).
Development of analogues of 1alpha,25-dihydroxyvitamin D3 with biased side chain orientation: methylated des-C,D-homo analogues.
  Chemistry, 7, 520-532.  
11585812 S.Mackem, C.T.Baumann, and G.L.Hager (2001).
A glucocorticoid/retinoic acid receptor chimera that displays cytoplasmic/nuclear translocation in response to retinoic acid. A real time sensing assay for nuclear receptor ligands.
  J Biol Chem, 276, 45501-45504.  
11731293 T.Fujishima, K.Konno, K.Nakagawa, M.Tanaka, T.Okano, M.Kurihara, N.Miyata, and H.Takayama (2001).
Synthesis and biological evaluation of all A-ring stereoisomers of 5,6-trans-2-methyl-1,25-dihydroxyvitamin D(3) and their 20-epimers: possible binding modes of potent A-ring analogues to vitamin D receptor.
  Chem Biol, 8, 1011-1024.  
11607933 U.Egner, N.Heinrich, M.Ruff, M.Gangloff, A.Mueller-Fahrnow, and J.M.Wurtz (2001).
Different ligands-different receptor conformations: modeling of the hER alpha LBD in complex with agonists and antagonists.
  Med Res Rev, 21, 523-539.  
11348471 Y.Bury, D.Ruf, C.M.Hansen, A.M.Kissmeyer, L.Binderup, and C.Carlberg (2001).
Molecular evaluation of vitamin D3 receptor agonists designed for topical treatment of skin diseases.
  J Invest Dermatol, 116, 785-792.  
11358696 Y.Shi, and J.T.Koh (2001).
Selective regulation of gene expression by an orthogonal estrogen receptor-ligand pair created by polar-group exchange.
  Chem Biol, 8, 501-510.  
10744685 G.Mengus, Y.G.Gangloff, L.Carré, A.C.Lavigne, and I.Davidson (2000).
The human transcription factor IID subunit human TATA-binding protein-associated factor 28 interacts in a ligand-reversible manner with the vitamin D(3) and thyroid hormone receptors.
  J Biol Chem, 275, 10064-10071.  
  10892801 J.M.Wurtz, B.Guillot, J.Fagart, D.Moras, K.Tietjen, and M.Schindler (2000).
A new model for 20-hydroxyecdysone and dibenzoylhydrazine binding: a homology modeling and docking approach.
  Protein Sci, 9, 1073-1084.  
11015194 N.Swamy, W.Xu, N.Paz, J.C.Hsieh, M.R.Haussler, G.J.Maalouf, S.C.Mohr, and R.Ray (2000).
Molecular modeling, affinity labeling, and site-directed mutagenesis define the key points of interaction between the ligand-binding domain of the vitamin D nuclear receptor and 1 alpha,25-dihydroxyvitamin D3.
  Biochemistry, 39, 12162-12171.  
10835357 P.F.Egea, A.Mitschler, N.Rochel, M.Ruff, P.Chambon, and D.Moras (2000).
Crystal structure of the human RXRalpha ligand-binding domain bound to its natural ligand: 9-cis retinoic acid.
  EMBO J, 19, 2592-2601.
PDB code: 1fby
10983973 P.Pissios, I.Tzameli, P.Kushner, and D.D.Moore (2000).
Dynamic stabilization of nuclear receptor ligand binding domains by hormone or corepressor binding.
  Mol Cell, 6, 245-253.  
11050318 W.Bourguet, P.Germain, and H.Gronemeyer (2000).
Nuclear receptor ligand-binding domains: three-dimensional structures, molecular interactions and pharmacological implications.
  Trends Pharmacol Sci, 21, 381-388.  
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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