PDBsum entry 1a28

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Progesterone receptor PDB id
Protein chain
251 a.a. *
STR ×2
Waters ×180
* Residue conservation analysis
PDB id:
Name: Progesterone receptor
Title: Hormone-bound human progesterone receptor ligand-binding domain
Structure: Progesterone receptor. Chain: a, b. Fragment: ligand binding domain. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: t47-d. Gene: pgr. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693. Other_details: breast cancer
1.80Å     R-factor:   0.191     R-free:   0.227
Authors: P.B.Sigler,S.P.Williams
Key ref:
S.P.Williams and P.B.Sigler (1998). Atomic structure of progesterone complexed with its receptor. Nature, 393, 392-396. PubMed id: 9620806 DOI: 10.1038/30775
19-Jan-98     Release date:   15-Jul-98    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P06401  (PRGR_HUMAN) -  Progesterone receptor
933 a.a.
251 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: 10.1038/30775 Nature 393:392-396 (1998)
PubMed id: 9620806  
Atomic structure of progesterone complexed with its receptor.
S.P.Williams, P.B.Sigler.
The physiological effects of progestins are mediated by the progesterone receptor, a member of the steroid/nuclear receptor superfamily. As progesterone is required for maintenance of pregnancy, its receptor has been a target for pharmaceuticals. Here we report the 1.8 A crystal structure of a progesterone-bound ligand-binding domain of the human progesterone receptor. The nature of this structure explains the receptor's selective affinity for progestins and establishes a common mode of recognition of 3-oxy steroids by the cognate receptors. Although the overall fold of the progesterone receptor is similar to that found in related receptors, the progesterone receptor has a quite different mode of dimerization. A hormone-induced stabilization of the carboxy-terminal secondary structure of the ligand-binding domain of the progesterone receptor accounts for the stereochemistry of this distinctive dimer, explains the receptor's characteristic pattern of ligand-dependent protease resistance and its loss of repression, and indicates how the anti-progestin RU486 might work in birth control. The structure also indicates that the analogous 3-keto-steroid receptors may have a similar mechanism of action.
  Selected figure(s)  
Figure 2.
Figure 2 The progesterone-binding pocket. a, Stereo view of the electron density (sigmaA weighted 2F[o]-F[c] at 1.8 ┼ resolution) of the bound progesterone and surrounding residues contoured at 1.7 superimposed on the refined model. b, space-filling CPK representation of the hormone-binding pocket; carbon, nitrogen and oxygen atoms are grey, blue and red, respectively. Bound progesterone carbon atoms are cyan and oxygen atoms are green. c, Hydrogen-bonding network that serves as the specificity determinant for the 3-oxy function of progesterone. Hydrogen-bond lengths are in ┼. Dashed lines indicate the connectivity of residues 777 and 778. The amido-keto interaction is predicted on the basis of the structure of the ER LBD complexes and sequence homology6. d, Interactions between the PR LBD and bound progesterone (centre). Hydrogen bonds are indicated by solid arrows, and van der Waals contacts (4 ┼ cutoff) by dashed lines.
Figure 3.
Figure 3 Comparison of the PR LBD and RXR LBD dimers. Dashed ends of RXR indicate truncation of the C-terminal five amino acids. Residues in the PR LBD that form the interface are shown at the top. Dashed lines at the top indicate van der Waals contacts (4 ┼ cutoff), and arrows indicate hydrogen bonds. There is also a van der Waals contact between residues Ala 922 and Leu 921.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (1998, 393, 392-396) copyright 1998.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20692346 J.J.Kerrigan, Q.Xie, R.S.Ames, and Q.Lu (2011).
Production of protein complexes via co-expression.
  Protein Expr Purif, 75, 1.  
20673774 R.E.Hubbard (2011).
Structure-based drug discovery and protein targets in the CNS.
  Neuropharmacology, 60, 7.  
20333619 A.S.Veleiro, L.D.Alvarez, S.L.Eduardo, and G.Burton (2010).
Structure of the glucocorticoid receptor, a flexible protein that can adapt to different ligands.
  ChemMedChem, 5, 649-659.  
20547846 E.P.Stout, J.J.La Clair, T.W.Snell, T.L.Shearer, and J.Kubanek (2010).
Conservation of progesterone hormone function in invertebrate reproduction.
  Proc Natl Acad Sci U S A, 107, 11859-11864.  
19919846 J.Kopecek, and P.Kopecková (2010).
HPMA copolymers: origins, early developments, present, and future.
  Adv Drug Deliv Rev, 62, 122-149.  
20723571 L.Jin, and Y.Li (2010).
Structural and functional insights into nuclear receptor signaling.
  Adv Drug Deliv Rev, 62, 1218-1226.  
20817759 R.Goyanka, S.Das, H.H.Samuels, and T.Cardozo (2010).
Nuclear receptor engineering based on novel structure activity relationships revealed by farnesyl pyrophosphate.
  Protein Eng Des Sel, 23, 809-815.  
19741205 R.N.Hanna, S.C.Daly, Y.Pang, I.Anglade, O.Kah, P.Thomas, and Y.Zhu (2010).
Characterization and expression of the nuclear progestin receptor in zebrafish gonads and brain.
  Biol Reprod, 82, 112-122.  
20624985 T.Frisci─ç, R.W.Lancaster, L.Fábián, and P.G.Karamertzanis (2010).
Tunable recognition of the steroid alpha-face by adjacent pi-electron density.
  Proc Natl Acad Sci U S A, 107, 13216-13221.  
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.  
19362102 C.Byrne, S.D.Divekar, G.B.Storchan, D.A.Parodi, and M.B.Martin (2009).
Cadmium--a metallohormone?
  Toxicol Appl Pharmacol, 238, 266-271.  
19721807 G.N.Brooke, and C.L.Bevan (2009).
The role of androgen receptor mutations in prostate cancer progression.
  Curr Genomics, 10, 18-25.  
19372222 H.C.Raaijmakers, J.E.Versteegh, and J.C.Uitdehaag (2009).
The X-ray Structure of RU486 Bound to the Progesterone Receptor in a Destabilized Agonistic Conformation.
  J Biol Chem, 284, 19572-19579.
PDB code: 2w8y
19557178 M.E.Baker, D.J.Chang, and C.Chandsawangbhuwana (2009).
3D model of lamprey estrogen receptor with estradiol and 15alpha-hydroxy-estradiol.
  PLoS One, 4, e6038.  
19702782 P.Li, A.K.Bandyopadhyaya, D.F.Covey, J.H.Steinbach, and G.Akk (2009).
Hydrogen bonding between the 17beta-substituent of a neurosteroid and the GABA(A) receptor is not obligatory for channel potentiation.
  Br J Pharmacol, 158, 1322-1329.  
19666041 R.Kumar, and G.Litwack (2009).
Structural and functional relationships of the steroid hormone receptors' N-terminal transactivation domain.
  Steroids, 74, 877-883.  
19333551 S.Ellmann, H.Sticht, F.Thiel, M.W.Beckmann, R.Strick, and P.L.Strissel (2009).
Estrogen and progesterone receptors: from molecular structures to clinical targets.
  Cell Mol Life Sci, 66, 2405-2426.  
19633971 T.Kino, Y.A.Su, and G.P.Chrousos (2009).
Human glucocorticoid receptor isoform beta: recent understanding of its potential implications in physiology and pathophysiology.
  Cell Mol Life Sci, 66, 3435-3448.  
18363044 D.F.Skafar, and C.Zhao (2008).
The multifunctional estrogen receptor-alpha F domain.
  Endocrine, 33, 1-8.  
17936318 G.A.Morrill, A.B.Kostellow, and A.Askari (2008).
Progesterone binding to the alpha1-subunit of the Na/K-ATPase on the cell surface: insights from computational modeling.
  Steroids, 73, 27-40.  
18622097 H.Kagechika (2008).
[Chemical biology research on nuclear receptors]
  Nippon Yakurigaku Zasshi, 132, 11-17.  
18502379 J.Zhang, and D.S.Geller (2008).
Helix 3-helix 5 interactions in steroid hormone receptor function.
  J Steroid Biochem Mol Biol, 109, 279-285.  
18160712 K.Suino-Powell, Y.Xu, C.Zhang, Y.G.Tao, W.D.Tolbert, S.S.Simons, and H.E.Xu (2008).
Doubling the size of the glucocorticoid receptor ligand binding pocket by deacylcortivazol.
  Mol Cell Biol, 28, 1915-1923.
PDB code: 3bqd
18815806 M.Schubert, F.Brunet, M.Paris, S.Bertrand, G.Benoit, and V.Laudet (2008).
Nuclear hormone receptor signaling in amphioxus.
  Dev Genes Evol, 218, 651-665.  
18330543 T.Harada, K.Yamagishi, T.Nakano, K.Kitaura, and H.Tokiwa (2008).
Ab initio fragment molecular orbital study of ligand binding to human progesterone receptor ligand-binding domain.
  Naunyn Schmiedebergs Arch Pharmacol, 377, 607-615.  
18578507 Y.G.Tao, Y.Xu, H.E.Xu, and S.S.Simons (2008).
Mutations of glucocorticoid receptor differentially affect AF2 domain activity in a steroid-selective manner to alter the potency and efficacy of gene induction and repression.
  Biochemistry, 47, 7648-7662.  
18350282 Y.Umezawa (2008).
Detecting mitochondrial RNA and other cellular events in living cells.
  Anal Bioanal Chem, 391, 1591-1598.  
20636084 Y.Umezawa (2008).
Optical probes for molecular processes in live cells.
  Annu Rev Anal Chem (Palo Alto Calif), 1, 397-421.  
17164529 A.M.Hassell, G.An, R.K.Bledsoe, J.M.Bynum, H.L.Carter, S.J.Deng, R.T.Gampe, T.E.Grisard, K.P.Madauss, R.T.Nolte, W.J.Rocque, L.Wang, K.L.Weaver, S.P.Williams, G.B.Wisely, R.Xu, and L.M.Shewchuk (2007).
Crystallization of protein-ligand complexes.
  Acta Crystallogr D Biol Crystallogr, 63, 72-79.  
17137423 D.L.Bain, A.F.Heneghan, K.D.Connaghan-Jones, and M.T.Miura (2007).
Nuclear receptor structure: implications for function.
  Annu Rev Physiol, 69, 201-220.  
17656319 J.Lee, J.E.Burdette, K.W.MacRenaris, D.Mustafi, T.K.Woodruff, and T.J.Meade (2007).
Rational design, synthesis, and biological evaluation of progesterone-modified MRI contrast agents.
  Chem Biol, 14, 824-834.  
17013809 K.P.Madauss, E.L.Stewart, and S.P.Williams (2007).
The evolution of progesterone receptor ligands.
  Med Res Rev, 27, 374-400.  
17468738 K.W.Nettles, J.B.Bruning, G.Gil, E.E.O'Neill, J.Nowak, Y.Guo, A.Hughs, Y.Kim, E.R.DeSombre, R.Dilis, R.N.Hanson, A.Joachimiak, and G.L.Greene (2007).
Structural plasticity in the oestrogen receptor ligand-binding domain.
  EMBO Rep, 8, 563-568.
PDB code: 2p15
17387660 M.Awais, M.Sato, and Y.Umezawa (2007).
Imaging of selective nuclear receptor modulator-induced conformational changes in the nuclear receptor to allow interaction with coactivator and corepressor proteins in living cells.
  Chembiochem, 8, 737-743.  
17306029 M.E.Baker, C.Chandsawangbhuwana, and N.Ollikainen (2007).
Structural analysis of the evolution of steroid specificity in the mineralocorticoid and glucocorticoid receptors.
  BMC Evol Biol, 7, 24.  
17261597 S.H.Meijsing, C.Elbi, H.F.Luecke, G.L.Hager, and K.R.Yamamoto (2007).
The ligand binding domain controls glucocorticoid receptor dynamics independent of ligand release.
  Mol Cell Biol, 27, 2442-2451.  
16714764 B.R.Keppler, A.T.Grady, and M.B.Jarstfer (2006).
The biochemical role of the heat shock protein 90 chaperone complex in establishing human telomerase activity.
  J Biol Chem, 281, 19840-19848.  
16892386 J.T.Moore, J.L.Collins, and K.H.Pearce (2006).
The nuclear receptor superfamily and drug discovery.
  ChemMedChem, 1, 504-523.  
16641486 K.Pereira de Jésus-Tran, P.L.Côté, L.Cantin, J.Blanchet, F.Labrie, and R.Breton (2006).
Comparison of crystal structures of human androgen receptor ligand-binding domain complexed with various agonists reveals molecular determinants responsible for binding affinity.
  Protein Sci, 15, 987-999.
PDB codes: 2am9 2ama 2amb
16528529 L.Rickardson, M.Fryknäs, C.Haglund, H.Lövborg, P.Nygren, M.G.Gustafsson, A.Isaksson, and R.Larsson (2006).
Screening of an annotated compound library for drug activity in a resistant myeloma cell line.
  Cancer Chemother Pharmacol, 58, 749-758.  
16854979 N.S.Cintron, and D.Toft (2006).
Defining the requirements for Hsp40 and Hsp70 in the Hsp90 chaperone pathway.
  J Biol Chem, 281, 26235-26244.  
16914190 P.Ascenzi, A.Bocedi, and M.Marino (2006).
Structure-function relationship of estrogen receptor alpha and beta: impact on human health.
  Mol Aspects Med, 27, 299-402.  
16204887 J.Aishima, D.S.Russel, L.J.Guibas, P.D.Adams, and A.T.Brunger (2005).
Automated crystallographic ligand building using the medial axis transform of an electron-density isosurface.
  Acta Crystallogr D Biol Crystallogr, 61, 1354-1363.  
15908963 J.Fagart, J.Huyet, G.M.Pinon, M.Rochel, C.Mayer, and M.E.Rafestin-Oblin (2005).
Crystal structure of a mutant mineralocorticoid receptor responsible for hypertension.
  Nat Struct Mol Biol, 12, 554-555.
PDB codes: 1y9r 1ya3
15710879 J.Zhang, J.Simisky, F.T.Tsai, and D.S.Geller (2005).
A critical role of helix 3-helix 5 interaction in steroid hormone receptor function.
  Proc Natl Acad Sci U S A, 102, 2707-2712.  
15883974 J.von Langen, K.H.Fritzemeier, S.Diekmann, and A.Hillisch (2005).
Molecular basis of the interaction specificity between the human glucocorticoid receptor and its endogenous steroid ligand cortisol.
  Chembiochem, 6, 1110-1118.  
16419642 K.Kamide, J.Yang, Y.Kokubo, S.Takiuchi, Y.Miwa, T.Horio, C.Tanaka, M.Banno, J.Nagura, A.Okayama, H.Tomoike, Y.Kawano, and T.Miyata (2005).
A novel missense mutation, F826Y, in the mineralocorticoid receptor gene in Japanese hypertensives: its implications for clinical phenotypes.
  Hypertens Res, 28, 703-709.  
16244724 M.Cacciarini, V.A.Azov, P.Seiler, H.Künzer, and F.Diederich (2005).
Selective steroid recognition by a partially bridged resorcin[4]arene cavitand.
  Chem Commun (Camb), (), 5269-5271.  
16351736 P.D'Ursi, E.Salvi, P.Fossa, L.Milanesi, and E.Rovida (2005).
Modelling the interaction of steroid receptors with endocrine disrupting chemicals.
  BMC Bioinformatics, 6, S10.  
16359432 R.J.Fletterick (2005).
Molecular modelling of the androgen receptor axis: rational basis for androgen receptor intervention in androgen-independent prostate cancer.
  BJU Int, 96, 2-9.  
15967794 R.K.Bledsoe, K.P.Madauss, J.A.Holt, C.J.Apolito, M.H.Lambert, K.H.Pearce, T.B.Stanley, E.L.Stewart, R.P.Trump, T.M.Willson, and S.P.Williams (2005).
A ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptor.
  J Biol Chem, 280, 31283-31293.
PDB codes: 2aa2 2aa5 2aa6 2aa7 2aax 2ab2
16061183 Y.Li, K.Suino, J.Daugherty, and H.E.Xu (2005).
Structural and biochemical mechanisms for the specificity of hormone binding and coactivator assembly by mineralocorticoid receptor.
  Mol Cell, 19, 367-380.
PDB code: 2a3i
15937332 Z.Zhang, A.M.Olland, Y.Zhu, J.Cohen, T.Berrodin, S.Chippari, C.Appavu, S.Li, J.Wilhem, R.Chopra, A.Fensome, P.Zhang, J.Wrobel, R.J.Unwalla, C.R.Lyttle, and R.C.Winneker (2005).
Molecular and pharmacological properties of a potent and selective novel nonsteroidal progesterone receptor agonist tanaproget.
  J Biol Chem, 280, 28468-28475.
PDB code: 1zuc
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.  
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
14977406 M.L.Privalsky (2004).
The role of corepressors in transcriptional regulation by nuclear hormone receptors.
  Annu Rev Physiol, 66, 315-360.  
15572776 P.H.Zwart, G.G.Langer, and V.S.Lamzin (2004).
Modelling bound ligands in protein crystal structures.
  Acta Crystallogr D Biol Crystallogr, 60, 2230-2239.  
15109611 P.J.Fuller (2004).
Aldosterone and DNA: the 50th anniversary.
  Trends Endocrinol Metab, 15, 143-146.  
15105832 Y.Brelivet, S.Kammerer, N.Rochel, O.Poch, and D.Moras (2004).
Signature of the oligomeric behaviour of nuclear receptors at the sequence and structural level.
  EMBO Rep, 5, 423-429.  
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.  
12612084 B.He, and E.M.Wilson (2003).
Electrostatic modulation in steroid receptor recruitment of LXXLL and FXXLF motifs.
  Mol Cell Biol, 23, 2135-2150.  
12686538 B.Kauppi, C.Jakob, M.Färnegårdh, J.Yang, H.Ahola, M.Alarcon, K.Calles, O.Engström, J.Harlan, S.Muchmore, A.K.Ramqvist, S.Thorell, L.Ohman, J.Greer, J.A.Gustafsson, J.Carlstedt-Duke, and M.Carlquist (2003).
The three-dimensional structures of antagonistic and agonistic forms of the glucocorticoid receptor ligand-binding domain: RU-486 induces a transconformation that leads to active antagonism.
  J Biol Chem, 278, 22748-22754.
PDB codes: 1nhz 1p93
12559765 B.M.Necela, and J.A.Cidlowski (2003).
Crystallization of the human glucocorticoid receptor ligand binding domain: a step towards selective glucocorticoids.
  Trends Pharmacol Sci, 24, 58-61.  
12714604 C.L.Hsu, Y.L.Chen, S.Yeh, H.J.Ting, Y.C.Hu, H.Lin, X.Wang, and C.Chang (2003).
The use of phage display technique for the isolation of androgen receptor interacting peptides with (F/W)XXL(F/W) and FXXLY new signature motifs.
  J Biol Chem, 278, 23691-23698.  
12771131 I.U.Agoulnik, W.C.Krause, W.E.Bingman, H.T.Rahman, M.Amrikachi, G.E.Ayala, and N.L.Weigel (2003).
Repressors of androgen and progesterone receptor action.
  J Biol Chem, 278, 31136-31148.  
12579585 K.Nam, P.Marshall, R.M.Wolf, and W.Cornell (2003).
Simulation of the different biological activities of diethylstilbestrol (DES) on estrogen receptor alpha and estrogen-related receptor gamma.
  Biopolymers, 68, 130-138.  
12819202 M.Färnegårdh, T.Bonn, S.Sun, J.Ljunggren, H.Ahola, A.Wilhelmsson, J.A.Gustafsson, and M.Carlquist (2003).
The three-dimensional structure of the liver X receptor beta reveals a flexible ligand-binding pocket that can accommodate fundamentally different ligands.
  J Biol Chem, 278, 38821-38828.
PDB codes: 1pq6 1pq9 1pqc
12773573 M.R.Yudt, C.M.Jewell, R.J.Bienstock, and J.A.Cidlowski (2003).
Molecular origins for the dominant negative function of human glucocorticoid receptor beta.
  Mol Cell Biol, 23, 4319-4330.  
12970175 S.Svensson, T.Ostberg, M.Jacobsson, C.Norström, K.Stefansson, D.Hallén, I.C.Johansson, K.Zachrisson, D.Ogg, and L.Jendeberg (2003).
Crystal structure of the heterodimeric complex of LXRalpha and RXRbeta ligand-binding domains in a fully agonistic conformation.
  EMBO J, 22, 4625-4633.
PDB code: 1uhl
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.  
12616628 T.Mordasini, A.Curioni, R.Bursi, and W.Andreoni (2003).
The binding mode of progesterone to its receptor deduced from molecular dynamics simulations.
  Chembiochem, 4, 155-161.  
12556447 V.H.Coulthard, S.Matsuda, and D.M.Heery (2003).
An extended LXXLL motif sequence determines the nuclear receptor binding specificity of TRAP220.
  J Biol Chem, 278, 10942-10951.  
12663754 X.Wang, X.Qian, H.C.Guo, and J.Hu (2003).
Heat shock protein 90-independent activation of truncated hepadnavirus reverse transcriptase.
  J Virol, 77, 4471-4480.  
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.  
12077419 B.C.Freeman, and K.R.Yamamoto (2002).
Disassembly of transcriptional regulatory complexes by molecular chaperones.
  Science, 296, 2232-2235.  
12220494 G.B.Wisely, A.B.Miller, R.G.Davis, A.D.Thornquest, R.Johnson, T.Spitzer, A.Sefler, B.Shearer, J.T.Moore, A.B.Miller, T.M.Willson, and S.P.Williams (2002).
Hepatocyte nuclear factor 4 is a transcription factor that constitutively binds fatty acids.
  Structure, 10, 1225-1234.
PDB code: 1lv2
12481024 I.Rogatsky, H.F.Luecke, D.C.Leitman, and K.R.Yamamoto (2002).
Alternate surfaces of transcriptional coregulator GRIP1 function in different glucocorticoid receptor activation and repression contexts.
  Proc Natl Acad Sci U S A, 99, 16701-16706.  
11877418 J.A.Tan, S.H.Hall, K.G.Hamil, G.Grossman, P.Petrusz, and F.S.French (2002).
Protein inhibitors of activated STAT resemble scaffold attachment factors and function as interacting nuclear receptor coregulators.
  J Biol Chem, 277, 16993-17001.  
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.  
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.  
12145311 S.Kaul, P.J.Murphy, J.Chen, L.Brown, W.B.Pratt, and S.S.Simons (2002).
Mutations at positions 547-553 of rat glucocorticoid receptors reveal that hsp90 binding requires the presence, but not defined composition, of a seven-amino acid sequence at the amino terminus of the ligand binding domain.
  J Biol Chem, 277, 36223-36232.  
12118039 T.Kucera, M.Waltner-Law, D.K.Scott, R.Prasad, and D.K.Granner (2002).
A point mutation of the AF2 transactivation domain of the glucocorticoid receptor disrupts its interaction with steroid receptor coactivator 1.
  J Biol Chem, 277, 26098-26102.  
  12537557 W.Mifsud, and A.Bateman (2002).
Membrane-bound progesterone receptors contain a cytochrome b5-like ligand-binding domain.
  Genome Biol, 3, RESEARCH0068.  
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.  
11343920 B.C.Freeman, and K.R.Yamamoto (2001).
Continuous recycling: a mechanism for modulatory signal transduction.
  Trends Biochem Sci, 26, 285-290.  
11456479 B.Tahiri, G.Auzou, J.C.Nicolas, C.Sultan, and B.Lupo (2001).
Participation of critical residues from the extreme C-terminal end of the human androgen receptor in the ligand binding function.
  Biochemistry, 40, 8431-8437.  
11157757 C.J.Schwartz, H.M.Sampson, D.Hlousek, A.Percival-Smith, J.W.Copeland, A.J.Simmonds, and H.M.Krause (2001).
FTZ-Factor1 and Fushi tarazu interact via conserved nuclear receptor and coactivator motifs.
  EMBO J, 20, 510-519.  
11496062 D.S.Geller (2001).
A mineralocorticoid receptor mutation causing human hypertension.
  Curr Opin Nephrol Hypertens, 10, 661-665.  
11353092 F.T.Wunderlich, H.Wildner, K.Rajewsky, and F.Edenhofer (2001).
New variants of inducible Cre recombinase: a novel mutant of Cre-PR fusion protein exhibits enhanced sensitivity and an expanded range of inducibility.
  Nucleic Acids Res, 29, E47.  
11689447 I.Rogatsky, K.A.Zarember, and K.R.Yamamoto (2001).
Factor recruitment and TIF2/GRIP1 corepressor activity at a collagenase-3 response element that mediates regulation by phorbol esters and hormones.
  EMBO J, 20, 6071-6083.  
11154266 J.G.Savory, G.G.Préfontaine, C.Lamprecht, M.Liao, R.F.Walther, Y.A.Lefebvre, and R.J.Haché (2001).
Glucocorticoid receptor homodimers and glucocorticoid-mineralocorticoid receptor heterodimers form in the cytoplasm through alternative dimerization interfaces.
  Mol Cell Biol, 21, 781-793.  
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
11331759 J.W.Thornton (2001).
Evolution of vertebrate steroid receptors from an ancestral estrogen receptor by ligand exploitation and serial genome expansions.
  Proc Natl Acad Sci U S A, 98, 5671-5676.  
11744099 M.Schumacher, R.Guennoun, G.Mercier, F.Désarnaud, P.Lacor, J.Bénavides, B.Ferzaz, F.Robert, and E.E.Baulieu (2001).
Progesterone synthesis and myelin formation in peripheral nerves.
  Brain Res Brain Res Rev, 37, 343-359.  
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.  
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.  
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.  
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.  
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.  
11553641 Y.Yamamoto, O.Wada, M.Suzawa, Y.Yogiashi, T.Yano, S.Kato, and J.Yanagisawa (2001).
The tamoxifen-responsive estrogen receptor alpha mutant D351Y shows reduced tamoxifen-dependent interaction with corepressor complexes.
  J Biol Chem, 276, 42684-42691.  
10722692 A.Chauchereau, M.Georgiakaki, M.Perrin-Wolff, E.Milgrom, and H.Loosfelt (2000).
JAB1 interacts with both the progesterone receptor and SRC-1.
  J Biol Chem, 275, 8540-8548.  
10744339 A.J.Oakley, and M.C.Wilce (2000).
Macromolecular crystallography as a tool for investigating drug, enzyme and receptor interactions.
  Clin Exp Pharmacol Physiol, 27, 145-151.  
10760050 C.Hellal-Levy, J.Fagart, A.Souque, and M.E.Rafestin-Oblin (2000).
Mechanistic aspects of mineralocorticoid receptor activation.
  Kidney Int, 57, 1250-1255.  
10734072 D.K.Lee, H.O.Duan, and C.Chang (2000).
From androgen receptor to the general transcription factor TFIIH. Identification of cdk activating kinase (CAK) as an androgen receptor NH(2)-terminal associated coactivator.
  J Biol Chem, 275, 9308-9313.  
10884226 D.S.Geller, A.Farhi, N.Pinkerton, M.Fradley, M.Moritz, A.Spitzer, G.Meinke, F.T.Tsai, P.B.Sigler, and R.P.Lifton (2000).
Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy.
  Science, 289, 119-123.  
  10757764 G.E.Carney, and M.Bender (2000).
The Drosophila ecdysone receptor (EcR) gene is required maternally for normal oogenesis.
  Genetics, 154, 1203-1211.  
10757780 I.Tzameli, P.Pissios, E.G.Schuetz, and D.D.Moore (2000).
The xenobiotic compound 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene is an agonist ligand for the nuclear receptor CAR.
  Mol Cell Biol, 20, 2951-2958.  
  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.  
10845098 J.Zhang, and M.A.Lazar (2000).
The mechanism of action of thyroid hormones.
  Annu Rev Physiol, 62, 439-466.  
10677485 K.Yamamoto, H.Masuno, M.Choi, K.Nakashima, T.Taga, H.Ooizumi, K.Umesono, W.Sicinska, J.VanHooke, H.F.DeLuca, and S.Yamada (2000).
Three-dimensional modeling of and ligand docking to vitamin D receptor ligand binding domain.
  Proc Natl Acad Sci U S A, 97, 1467-1472.  
11250728 M.Ruff, M.Gangloff, J.M.Wurtz, and D.Moras (2000).
Estrogen receptor transcription and transactivation: Structure-function relationship in DNA- and ligand-binding domains of estrogen receptors.
  Breast Cancer Res, 2, 353-359.  
10655475 M.Schapira, B.M.Raaka, H.H.Samuels, and R.Abagyan (2000).
Rational discovery of novel nuclear hormone receptor antagonists.
  Proc Natl Acad Sci U S A, 97, 1008-1013.  
10678179 N.Rochel, J.M.Wurtz, A.Mitschler, B.Klaholz, and D.Moras (2000).
The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand.
  Mol Cell, 5, 173-179.
PDB code: 1db1
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
11006480 R.Bursi, and M.B.Groen (2000).
Application of (quantitative) structure-activity relationships to progestagens: from serendipity to structure-based design.
  Eur J Med Chem, 35, 787-796.  
10882139 R.T.Gampe, V.G.Montana, M.H.Lambert, A.B.Miller, R.K.Bledsoe, M.V.Milburn, S.A.Kliewer, T.M.Willson, and H.E.Xu (2000).
Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors.
  Mol Cell, 5, 545-555.
PDB codes: 1fm6 1fm9
10970886 R.T.Gampe, V.G.Montana, M.H.Lambert, G.B.Wisely, M.V.Milburn, and H.E.Xu (2000).
Structural basis for autorepression of retinoid X receptor by tetramer formation and the AF-2 helix.
  Genes Dev, 14, 2229-2241.
PDB codes: 1g1u 1g5y
10867707 S.B.Nagl, S.Das, and T.F.Smith (2000).
Prediction of interaction partners for orphan nuclear receptors by prior-based protein sequence profiles.
  J Mol Recognit, 13, 117-126.  
10805730 S.F.Wang, S.Ayer, W.A.Segraves, D.R.Williams, and A.S.Raikhel (2000).
Molecular determinants of differential ligand sensitivities of insect ecdysteroid receptors.
  Mol Cell Biol, 20, 3870-3879.  
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.  
  10082574 A.Mouchon, M.H.Delmotte, P.Formstecher, and P.Lefebvre (1999).
Allosteric regulation of the discriminative responsiveness of retinoic acid receptor to natural and synthetic ligands by retinoid X receptor and DNA.
  Mol Cell Biol, 19, 3073-3085.  
10600690 A.Mueller-Fahrnow, and U.Egner (1999).
Ligand-binding domain of estrogen receptors.
  Curr Opin Biotechnol, 10, 550-556.  
10412035 A.W.Norman, D.Adams, E.D.Collins, W.H.Okamura, and R.J.Fletterick (1999).
Three-dimensional model of the ligand binding domain of the nuclear receptor for 1alpha,25-dihydroxy-vitamin D(3).
  J Cell Biochem, 74, 323-333.  
10601285 B.He, J.A.Kemppainen, J.J.Voegel, H.Gronemeyer, and E.M.Wilson (1999).
Activation function 2 in the human androgen receptor ligand binding domain mediates interdomain communication with the NH(2)-terminal domain.
  J Biol Chem, 274, 37219-37225.  
10410794 C.Wolberger (1999).
Multiprotein-DNA complexes in transcriptional regulation.
  Annu Rev Biophys Biomol Struct, 28, 29-56.  
9876133 D.Kosztin, S.Izrailev, and K.Schulten (1999).
Unbinding of retinoic acid from its receptor studied by steered molecular dynamics.
  Biophys J, 76, 188-197.  
10318858 D.M.Kraichely, J.J.Collins, R.K.DeLisle, and P.N.MacDonald (1999).
The autonomous transactivation domain in helix H3 of the vitamin D receptor is required for transactivation and coactivator interaction.
  J Biol Chem, 274, 14352-14358.  
10593921 F.M.Rogerson, N.Dimopoulos, P.Sluka, S.Chu, A.J.Curtis, and P.J.Fuller (1999).
Structural determinants of aldosterone binding selectivity in the mineralocorticoid receptor.
  J Biol Chem, 274, 36305-36311.  
  10490591 F.M.Sladek, M.D.Ruse, L.Nepomuceno, S.M.Huang, and M.R.Stallcup (1999).
Modulation of transcriptional activation and coactivator interaction by a splicing variation in the F domain of nuclear receptor hepatocyte nuclear factor 4alpha1.
  Mol Cell Biol, 19, 6509-6522.  
10593951 G.Giannoukos, A.M.Silverstein, W.B.Pratt, and S.S.Simons (1999).
The seven amino acids (547-553) of rat glucocorticoid receptor required for steroid and hsp90 binding contain a functionally independent LXXLL motif that is critical for steroid binding.
  J Biol Chem, 274, 36527-36536.  
10629110 G.K.Whitfield, P.W.Jurutka, C.A.Haussler, and M.R.Haussler (1999).
Steroid hormone receptors: evolution, ligands, and molecular basis of biologic function.
  J Cell Biochem, (), 110-122.  
10198642 H.E.Xu, M.H.Lambert, V.G.Montana, D.J.Parks, S.G.Blanchard, P.J.Brown, D.D.Sternbach, J.M.Lehmann, G.B.Wisely, T.M.Willson, S.A.Kliewer, and M.V.Milburn (1999).
Molecular recognition of fatty acids by peroxisome proliferator-activated receptors.
  Mol Cell, 3, 397-403.
PDB codes: 1gwx 2gwx 3gwx
9920895 H.Hong, B.D.Darimont, H.Ma, L.Yang, K.R.Yamamoto, and M.R.Stallcup (1999).
An additional region of coactivator GRIP1 required for interaction with the hormone-binding domains of a subset of nuclear receptors.
  J Biol Chem, 274, 3496-3502.  
10500147 H.Ma, and T.M.Penning (1999).
Conversion of mammalian 3alpha-hydroxysteroid dehydrogenase to 20alpha-hydroxysteroid dehydrogenase using loop chimeras: changing specificity from androgens to progestins.
  Proc Natl Acad Sci U S A, 96, 11161-11166.  
  10373553 I.Rogatsky, A.B.Hittelman, D.Pearce, and M.J.Garabedian (1999).
Distinct glucocorticoid receptor transcriptional regulatory surfaces mediate the cytotoxic and cytostatic effects of glucocorticoids.
  Mol Cell Biol, 19, 5036-5049.  
10230636 K.Yamamoto, H.Ooizumi, K.Umesono, A.Verstuyf, R.Bouillon, H.F.DeLuca, T.Shinki, T.Suda, and S.Yamada (1999).
Three-dimensional structure-function relationship of vitamin D: side chain location and various activities.
  Bioorg Med Chem Lett, 9, 1041-1046.  
  10567540 L.A.Sheldon, C.L.Smith, J.E.Bodwell, A.U.Munck, and G.L.Hager (1999).
A ligand binding domain mutation in the mouse glucocorticoid receptor functionally links chromatin remodeling and transcription initiation.
  Mol Cell Biol, 19, 8146-8157.  
9989224 M.Letz, P.Bringmann, M.Mann, A.Mueller-Fahrnow, D.Reipert, P.Scholz, J.M.Wurtz, and U.Egner (1999).
Investigation of the binding interactions of progesterone using muteins of the human progesterone receptor ligand binding domain designed on the basis of a three-dimensional protein model.
  Biochim Biophys Acta, 1429, 391-400.  
  10454556 P.Alen, F.Claessens, G.Verhoeven, W.Rombauts, and B.Peeters (1999).
The androgen receptor amino-terminal domain plays a key role in p160 coactivator-stimulated gene transcription.
  Mol Cell Biol, 19, 6085-6097.  
10591095 R.M.Knegtel, and M.Wagener (1999).
Efficacy and selectivity in flexible database docking.
  Proteins, 37, 334-345.  
10872460 R.V.Weatherman, R.J.Fletterick, and T.S.Scanlan (1999).
Nuclear-receptor ligands and ligand-binding domains.
  Annu Rev Biochem, 68, 559-581.  
9915825 S.H.Hong, and M.L.Privalsky (1999).
Retinoid isomers differ in the ability to induce release of SMRT corepressor from retinoic acid receptor-alpha.
  J Biol Chem, 274, 2885-2892.  
10567404 S.K.Lee, S.L.Anzick, J.E.Choi, L.Bubendorf, X.Y.Guan, Y.K.Jung, O.P.Kallioniemi, J.Kononen, J.M.Trent, D.Azorsa, B.H.Jhun, J.H.Cheong, Y.C.Lee, P.S.Meltzer, and J.W.Lee (1999).
A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo.
  J Biol Chem, 274, 34283-34293.  
10373460 U.Lind, P.Greenidge, J.A.Gustafsson, A.P.Wright, and J.Carlstedt-Duke (1999).
Valine 571 functions as a regional organizer in programming the glucocorticoid receptor for differential binding of glucocorticoids and mineralocorticoids.
  J Biol Chem, 274, 18515-18523.  
  9808622 B.D.Darimont, R.L.Wagner, J.W.Apriletti, M.R.Stallcup, P.J.Kushner, J.D.Baxter, R.J.Fletterick, and K.R.Yamamoto (1998).
Structure and specificity of nuclear receptor-coactivator interactions.
  Genes Dev, 12, 3343-3356.
PDB code: 1bsx
9813012 J.Uppenberg, C.Svensson, M.Jaki, G.Bertilsson, L.Jendeberg, and A.Berkenstam (1998).
Crystal structure of the ligand binding domain of the human nuclear receptor PPARgamma.
  J Biol Chem, 273, 31108-31112.
PDB code: 3prg
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 code is shown on the right.