Homology modelling of the nuclear receptors: Human oestrogen receptorβ (hERβ), the human pregnane-X-receptor (PXR)

Journal of Steroid Biochemistry and Molecular Biology

Volumn 84, Issue 2-3, 2003, Pages 117-132

  Jacobs, M N ^a   Dickins, M ^b   Lewis, D F V ^a  

^a UNIVERSITY OF SURREY   (United Kingdom)

^b GLAXOSMITHKLINE   (United Kingdom)

Author keywords

Ah receptor (AhR); Constitutive androstane receptor (CAR); Estrogen receptor (hER ); Ligand receptor interaction; Molecular modelling; Pregnane X receptor (PXR); Steroid hormone receptors (SHR)

Indexed keywords

ANDROSTANE DERIVATIVE; AROMATIC HYDROCARBON RECEPTOR; BINDING PROTEIN; CELL NUCLEUS RECEPTOR; CLOTRIMAZOLE; CONSTITUTIVE ANDROSTANE RECEPTOR; CORTICOSTERONE; COUMESTROL; DOCKING PROTEIN; ESTRADIOL; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; FATTY ACID; LIGAND; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PHYTOESTROGEN; PREGNANE X RECEPTOR; PREGNENOLONE; PROGESTERONE; PROGESTERONE RECEPTOR; RETINOID X RECEPTOR; STEROID RECEPTOR; TESTOSTERONE; THIAZOLIDINE DERIVATIVE; TRICLOSAN; UNCLASSIFIED DRUG; VITAMIN D RECEPTOR;

AMINO ACID SEQUENCE; BINDING COMPETITION; BINDING SITE; CONFERENCE PAPER; CRYSTAL STRUCTURE; CRYSTALLOGRAPHY; HORMONE INHIBITION; HORMONE RECEPTOR INTERACTION; HUMAN; HYDROGEN BOND; HYDROPHOBICITY; LIGAND BINDING; MOLECULAR MODEL; PROTEIN DOMAIN; PROTEIN EXPRESSION; SEQUENCE HOMOLOGY; STRUCTURE ANALYSIS;

EID: 0242417054     PISSN: 09600760     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-0760(03)00021-9     Document Type: Conference Paper

References (83)

1. Brzozowski A.M., Pike A.C., Dauter Z., Hubbard R.E., Bonn T., Engstrom O., Ohman L., Greene G.L., Gustafsson J.-Å., Carlqvist M. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature. 389:1997;753-758.
2. Mosselman S., Polman J., Dijkema R. ER beta: identification and characterization of a novel human estrogen receptor. FEBS Lett. 392:1996;49-53.
3. Lehmann J.M., McKee D.D., Watson M.A., Willson T.M., Moore J.T., Kliewer S.A. The human orphan nucler receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J. Clin. Invest. 102:1998;1016-1023.
4. Burbach K.M., Poland A., Bradfield C.A. Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor. Proc. Natl. Acad. Sci. U.S.A. 89:1992;815-819.
5. Forman B.M., Tzameli I., Choi H.-S., Chen J., Simha D., Seol W., Evans R.M., Moore D.D. Androstane metabolites bind to and deactivate the nuclear receptor CAR-β Nature. 395:1998;612-615.
6. Baes M., Gulick T., Choi H.-S., Martinoli M.G., Simha D., Moore D.D. A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements. Mol. Cell. Biol. 14:1994;1544-1552.
7. Lewis D.F.V., Lake B. Molecular modelling of the rat peroxisome proliferator-activated receptor α (rPPARα) by homology with the human retinoic acid X receptor α (hRARα) and investigation of peroxisome proliferator binding interactions: QSARs. Toxicol. In Vitro. 12:1998;619-632.
8. Nolte R.T., Wisely G.B., Westin S., Cobb J.E., Lambert M.H., Kurokawa R., Rosenfeld M.G., Willson T.M., Glass C.K., Milburn M.V. Ligand binding and co-activator assembly of the peroxisome proliferator-activated receptor-gamma. Nature. 395:1998;137-143.
9. Honkakoski P., Negishi M. Regulation of cytochrome P450 (CYP) genes by nuclear receptors. Biochem. J. 347:2000;321-337.
10. Weigel N. Steroid hormone receptors and their regulation by phosphorylation. Biochem. J. 319:1996;657-667.
11. Dennison M.S., Whitlock J.P. Jr. Xenobiotic-inducible transcription of cytochrome P450 genes. J. Biol. Chem. 270(41):1995;18175-18178.
12. Kliewer S.A., Lehmann J.M., Willson T.M. Orphan nuclear receptors: shifting endocrinology into reverse. Science. 284:1999;757-760.
13. Negishi M., Honkakoski P. Induction of drug metabolism by nuclear receptor CAR: molecular mechanisms and implications for drug research. Eur. J. Pharm. Sci. 11:2000;259-264.
14. Xie W., Evans R.M. Orphan nuclear receptors: the exotics of xenobiotics. J. Biol. Chem. 276:2001;37739-37742.
15. Nuclear Receptors Nomenclature Committee, A unified nomenclature system for the nuclear receptor superfamily, Cell 97 (1999) 161-163.
16. Willson T.M., Kliewer S.A. The Science of orphan nuclear receptors, Core findings, a gene-to-function approach to drug discovery. Odyssey. 6:2000;16-22.
17. Willson T.M., Brown P.J., Sternbach D.D., Henke B.R. The PPARs: from orphan receptors to drug discovery. J. Med. Chem. 43:2000;527-550.
18. McKenna N.J., Xu J., Nawaz Z., Tsai S.Y., Tsai M.-J., O'Malley B.W. Nuclear receptor coactivators: multiple enymes, multiple complexes, multiple functions. J. Steroid Biochem. Mol. Biol. 69:1999;3-12.
19. Cottone E., Orso F., Biglia N., Sisimondi P., De Bortoli M. Role of coactivators and corepressors in steroid and nuclear recptor signalling: potential markers of tomor growth and drug sensitivity. Int. J. Bio. Markers. 16(3):2001;151-166.
20. B. Alberts, D. Bray, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter, Essential Cell Biology, Garland publishing, New York, 1997.
21. Kenealy M.-R., Flouriot G., Sonntag-Buck V., Dandekar T., Brand H., Gannon F. The 3′untranslated region of the human estrogen receptor α gene mediates rapid messenger ribonucleic acid turnover. Endocrinology. 141:2000;2085-2813.
22. Lee H.-Y., Suh Y.-A., Robinson M.J., Clifford J.L., Hong W.K., Woodget J.R., Cobb M.H., Mangelsdorf D.J., Kurie J.M. Stress pathway activation induces phosphorylation of Retinoid X Receptor. J. Bio. Chem. 275:2000;32193-32199.
23. Sugatani J., Kojima H., Ueda A., Kakizaki S., Yoshinari K., Gong Q.-H., Owens I.S., Negishi M., Sueyoshi T. The phenobarbital response enhancer module in the human bilirubin UDP-glucuronosyltransferase UGT1A1 gene and regulation by the nuclear receptor CAR. Hepatology. 33:2001;1232-1238.
24. Synold T.W., Dussault I., Forman B.M. The orphan nuclear receptor SXR co-ordinately regulates drug metabolism and efflux. Nat. Med. 7:2001;584-590.
25. Nguyen T.A., Hoivik D., Lee J.-E., Safe S. Interactions of nuclear receptor coactivator/corepressor proteins with the aryl hydrocarbon receptor complex. Arch. Biochem. Biophys. 367:1999;250-257.
26. Jacobs M.N., Lewis D.F.V. Steroid hormone receptors and dietary ligands: a selected review. Proc. Nutr. Soc. 61:2002;105-122.
27. Petersen D.N., Tkalcevic G.T., Koza-Taylor P.H., Turi T.G., Brown T.A. Identification of estrogen receptor beta (2), a functional variant of estrogen receptor beta expressed in normal rat tissues. Endocrinology. 139:1998;1082-1092.
28. Kelley S.T., Thackray V.G. Phylogenetic analyses reveal ancient duplication of estrogen receptor isoforms. J. Mol. Evol. 49:1999;609-614.
29. Kuiper G.C.J.M., Lemmen J.G., Carlsson B., Corton J.C., Safe S.H., van der Saag P.T., van der Burg B., Gustafsson J.-Å. Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor ß Endocrinology. 139:1998;4252-4263.
30. Kuiper G.C.J.M., Carlsson B., Grandien K., Enmark E., Haggblad J., Nilsson S., Gustafsson J.Å. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology. 138:1997;863-870.
31. Hall J.M., McDonnell D.P. The Estrogen receptor β-isoform (ERβ) of the human estrogen receptor modulates ER α transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens. Endocrinology. 140:1999;5566-5578.
32. Fuqua S.A.W., Wiltschke C., Zhang Q.X., Borg Å., Castles C.G., Friedrichs W.E., Hopp T., Hilsenbeck S., Mohsin S., O'Connell P., Allred D.C. A hypersensitive estrogen receptor alpha mutation in premalignant breast lesions. Cancer Res. 60:2000;4026-4029.
33. Kliewer S.A., Moore J.T., Wade L., Staudinger J.L., Watson M.A., Jones S.A., McKee D.D., Oliver B.B., Willson T.M., Zetterström R.H., Perlmann T., Lehmann J.M. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell. 92:1998;73-82.
34. Blumberg B., Sabbagh W. Jr., Juguilon H., Bolado J. Jr., van Meter C.M., Ong E.S., Evans R.M. SXR, a novel steroid and xenobiotic-sensing nuclear receptor. Genes Develop. 12:1998;3195-3205.
35. Pascussi J.-M., Jounaidi Y., Drocourt L., Domergue J., Balabaud C., Maurel P., Vilarem M.-J. Evidence for the presence of a functional Pregnane X Receptor response element in the CYP3A7 promoter gene. Biochem. Biophys. Res. Commun. 260:1999;377-381.
36. P. Maurel, The CYP 3 family, in C. Ionnides (Ed.), Cytochromes P450: Metabolic and Toxicological Aspects, CRC Press Inc., Boca Raton, FL, 1996, pp. 241-270.
37. Jones S.A., Moore L.B., Shenk J.L., Wisely G.B., Hamilton G.A., McKee D.D., Tomkinson N.C.O., LeCluyse E.L., Lambert M.H., Willson T.M., Kliewer S.A., Moore J.T. The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. Mol. Endocrinol. 14:2000;27-39.
38. Dotzlaw H., Leygue E., Watson P., Murphy L.C. The human orphan receptor PXR messenger RNA is expressed in both normal and neoplastic breast tissue. Clin. Cancer Res. 8:1999;2103-2107.
39. Moore L.B., Goodwin B., Jones S.A., Wisely G.B., Willson T.M., Collins J.L., Kliewer S.A. St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc. Natl. Acad. Sci. U.S.A. 97:2000;7500-7502.
40. Moore L.B., Parks D.J., Jones S.A., Bledsoe R.K., Consler T.G., Stimmel J.B., Goodwin B., Liddle C., Blanchard S.G., Willson T.M., Collins J.L., Kliewer S.A. Orphan nuclear receptors constitutive androstane receptor and Pregnane X receptor share xenobiotic and steroid ligands. J. Biol. Chem. 275:2000;15122-15127.
41. Tzameli I., Moore D.D. Role reversal: new insights from new ligands for the xenobiotic receptor CAR. Trends Endocrinol. Metab. 12:2001;7-10.
42. Kawamoto T., Seuyoshi T., Zelko I., Moore R., Washburn K., Neigashi M. Phenobarbital-responsive nuclear translocation of the receptor CAR in induction of the CYP2B gene. Mol. Cell Biol. 19:1999;6318-6322.
43. Blumberg B., Evans R.M. Orphan nuclear receptors-new ligands and new possibilities. Genes Develop. 12:1998;3149-3155.
44. Swanson H.I., Bradfield C.A. The AH-receptor: genetics, structure and function. Pharmacogenetics. 3:1993;213-230.
45. Hahn M.E. The aryl hydrocarbon receptor: a comparative perspective. Comp. Biochem. Physiol. (C). 121:1998;23-53.
46. Nebert D.W., Eisen H.J., Negishi M., Lang M.A., Hjelmeland L.M., Okey A.B. Genetic mechanisms controlling the induction of polysubstrate monooxygenase (P-450) activities. Ann. Rev. Pharmacol. Toxicol. 21:1981;431-462.
47. Abbott B.D., Schmid J.E., Pitt J.A., Buckalew A.R., Wood C.R., Held G.A., Diliberto J.J. Adverse reproductive outcomes in the transgenic Ah receptor-deficient mouse. Toxicol. Appl. Pharmacol. 155:1999;62-70.
48. Sinal C.J., Bend R.J. Aryl hydroc arbon receptor-dependent induction of Cyp1a1 by bilirubin in mouse hepatatoma hepa 1c1c7 cells. Mol. Pharmacol. 52:1997;590-599.
49. Phelan D., Winter G.M., Lam J.C., Dennison M.S. Activation of the Ah receptor signal transduction pathway by bilirubin and biliverdin. Arch. Biochem. Biophys. 357(1):1998;155-163.
50. Gillner M., Bergman J., Ambilleau C., Feruström B., Gustafsson J.-Å. Interactions of indolo [3-2-6] carbazoles and related polycyclic aroma hydrocarbons with specific binding sites for 2,3,7,8-tetrachlorodobenzo-p-dioxin in rat liver. Mol. Pharmacol. 28:1993;336-345.
51. Heath-Pagliuso S., Rogers W.J., Tullis K., Seidel S.D., Cenijn P.H., Brouwer A., Denison M.S. Activation of the Ah receptor by tryptophan and tryptophan metabolites. Biochemistry. 37:1998;11508-11515.
52. Gambone C.J., Hutcheson J.M., Gabriel J.L., Beard R.L., Chandraaratna R.A.S., Soprano K.J., Robert Soprano D. Unique property of some synthetic retinoids: activation of the qryl hydrocarbon receptor pathway. Mol. Pharmacol. 61:2002;334-342.
53. S Dennison M., Phelan D., Winter G.M., Ziccardi M.H. Carbaryl, a carbamate insecticide is a ligand for the hepatic Ah (dioxin) Receptor. Toxicol. Appl. Pharmacol. 152:1998;406-414.
54. Van den Berg M., Birnbaum L., Bosveld A.T.C., Brünstrom B., Cook P., Feeley M., Giesy J.P., Hanberg A., Hasegawa R., Kennedy S.W., Kubiak T., Larsen J.C., van Leeuwen F.X.R., Liem A.K.D., Nolte C., Peterson R.E., Poellinger L., Safe S., Schrenk D., Tillit D., Tysklind M., Younes M., Wærn F., Zacharewski T. Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife. Env. Health Perspect. 106(12):1998;775-792.
55. Fernandez-Salugero P., Pinneau T., Hilbert D.M., McPhail T., Lee S.S.T., Kimura S., Nebert D.W., Rudikoff S., Ward J.M., Gonzalez F.J. Immune system impairment and hepatic fibrosis in mice lacking the dioxin binding Ah Receptor. Science. 268:1995;722-726.
56. Schmidt J.V., Su G.H.-I., Reddy J.K., Simon M.C., Bradfield C.A. Characterisation of a murine AhR null allele: involvement of the Ah receptor in hepatic growth and development. Proc. Natl. Acad. Sci. U.S.A. 93:1996;6731-6736.
57. Fernandez-Salugero P., Ward J.M., Sundberg J.P., Gonzalez F.J. Lesions of aryl-hydrocarbon receptor deficient mice. Vet. Pathol. 34:1997;605-614.
58. Diliberto J.J., Abbot B.D., Birnbaum L.S. Use of AhR knockout (AhR-/-) mice to investigate the role of the Ah receptor on the disposition of TCDD. Organohalogen Compounds. 49:2000;121-123.
59. Birnbaum L.S. Health effects of Dioxins: People are animals and vice versa ! Organohalogen Compounds. 49:2000;101-103.
60. Johnson T.E., Holloway M.K., Vogel R., Rutledge S.J., Perkins J.J., Rodan G.A., Scmidt A. Structural requirements and cell type specifity for ligand activation of peroxisome proliferator activated receptors. J. Steroid Biochem. Mol. Biol. 63:1997;1-8.
61. Uauy R., Mena P., Rojas C. Essential fatty acids in early life: structural and functional role. Proc. Nutr. Soc. 59:2000;3-15.
62. Bar-Tana J. Peroxisome proliferator-activated receptor gamma (PPARγ) activation and its consequences in humans. Toxicol. Letts. 120:2001;9-19.
63. Waxman D.J. P450 Gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR. Arch. Biochem. Biophys. 369:1999;11-23.
64. Chawla A., Repa J.J., Evans R.M., Mangelsdorf D.J. Nuclear receptors and lipid physiology: opening the X files. Science. 294:2001;1866-1870.
65. Xu H.E., Lambert M.H., Montana V.G., Parks D.J., Blanchard S.G., Brown P.J., Sternbach D.D., Lehmann J.M., Wisely G.B., Willson T.M., Kliewer S.A., Milburn M.V. Molecular recognition of fatty acids by peroxisome proliferator activated receptors. Mol. Cell. 3:1999;397-403.
66. Memon R.A., Tecott L.H., Nonogaki K., Beigneux A., Moser A.H., Grunfeld C., Feingold K.R. Up-regulation of peroxisome proliferator-activated receptor α (PPARα) and PPARγ Messenger ribonucleic acid expression in the liver in murine obesity: troglitazone induces expression of PPARγ responsive adipose tissue-specific genes in the liver of obese diabetic mice. Endocrinology. 141:2000;4021-4031.
67. Zomer A.W.M., van den Berg B., Jansen G.A., Wanders R.J.A., Tien Poll-The B., T van der Saag P. Pristanic acid and phytanic acid: naturally occurring ligands for the nuclear receptor peroxisome proliferator activated receptorα J. Lipid Res. 41:2000;1801-1807.
68. P. Cronet, J.F. Peterson, R. Folmer, N. Blomberg, K. Sjoblom, U. Karlson, E. Lindstedt, K. Bamberg, Structure of the PPAR alpha and gamma ligand binding domain in complex with AZ242; ligand selectivity and agonist activity in the PPAR family, Structure 9 (2001) 699-706.
69. Watkins R.E., Wisely G.B., Moore L.B., Collins J.L., Lambert M.H., Williams S.P., Willson T.M., Kleiwer S.A., Redinbo M.R. The human nuclear xenobiotic receptor PXR: structural determinants of directed promiscuity. Science. 292:2001;2329-2333.
70. Xu H.E., Lambert M.H., Montana V.G., Plunket K.D., Moore L.B., Collins J.L., Oplinger J.A., Kliewer S.A., Gampe Jr R.T., McKee D.D., Moore J.T., Willson T.M. Structural determinants of ligand binding specifricty between the peroxisome proliferator activated receptors. Proc. Nat. Acad. Sci. U.S.A. 98(24):2001;13919-13924.
71. Roberts R.A., James N.H., Woodyatt N.J., Macdonald N., Tugwood J.D. Evidence for the suppression of apoptosis by the peroxisome proliferator activated receptor alpha (PPAR alpha). Carcinogenesis. 19:1998;43-48.
72. Miyamoto T., Keneko A., Kakizawa T., Yajima H., Kamijo K., Sekine R., Hiramatsu K., Nishii Y., Hashimoto T., Hashizume K. Inhibition of peroxisome proliferator signaling pathways by thyroid hormone receptor - competitive binding to the response element. J. Biol. Chem. 272:1997;7752-7758.
73. Gaido K.W., Leonard L.S., Maness S.C., Hall J.M., McDonnell D.P., Saville B., Safe S. Differential interaction of the methoxychlor metabolite 2,2-bis-(p-hydroxyphenyl)-1,1,1-tricloroethane with estrogen receptors α and β Endocrinology. 140:1999;5746-5753.
74. Gustaffson J.-Å. The Role of the ERβ in oestrogen mediated carcinogenesis. Toxicol. Letts. 116:2000;1.
75. Jones S.A., Moore L.B., Shenk J.L., Wisely G.B., Hamilton G.A., McKee D.D., Tomkinson N.C.O., LeCluyse E.L., Lambert M.H., Willson T.M., Kliewer S.A., Moore J.T. The Pregnane X Receptor: a promiscuous xenobiotic receptor that has diverged during evolution. Mol. Endocrinol. 14:2000;27-39.
76. Barkhem T., Carlsson B., Nilsson Y., Enmark E., Gustafsson J-Å., Nilsson S. Differential response of estrogen receptor α and estrogen receptor β to partial estrogen agonists/antagonists. Mol. Pharmacol. 54:1998;105-112.
77. Fuqua S.A.W., Wiltschke C., Zhang Q.X., Borg Å., Castles C.G., Friedrichs W.E., Hopp T., Hilsenbeck S., Mohsin S., O'Connell P., Allred D.C. A hypersensitive estrogen receptor alpha mutation in premalignant breast lesions. Cancer Res. 60:2000;4026-4029.
78. Ekins S., Erickson J.A. A pharmacophore for human pregnane X receptor ligands. Drug Metab. Dispos. 30:2002;96-99.
79. Sueyoshi T., Kawamoto T., Zelko I., Honakakoshi P., Neigashi M. Phenobarbital-responsive enhancer module (PBREM) of human CYP2B6 gene and inducible transactivation by nuclear receptor CAR. J. Biol. Chem. 274:1999;6043-6046.
80. Pascussi J.-M., Gerbal-Chaloin S., Pichard-Garcia L., Daujat M., Fabre J.-M., Maurel P., Vilarem M.-J. Interleukin-6 negatively regulates the expression of pregnane X receptor and constitutively activated receptor in primary human hepatocytes. Biochem. Biophys. Res. Commun. 274:2000;707-713.
81. Lewis D.F.V., Jacobs M.N. A QSAR study of some PCBs ligand-binding affinity to the cytosolic Ah Receptor. Organohalogen Comp. 41:1999;537-540.
82. Pike A.C.W., Brzozowski A.M., Hubbard R.E., Bonn T., Thorsell A.-G., Engström O., Ljunggren J., Gustafsson J.-Å., Carlquist M. Structure of the ligand-binding domain of oestrogen receptor beta in the presence of a partial agonist and a full agonist. EMBO J. 18:1999;4608-4618.
83. Xu H.E., Stanley T.B., Montana V.G., Lambert M.H., Shearer B.G., Cobb J.E., McKee D.D., Galardi C.M., Plunket K.D., Nolte R.T., Parks D.J., Moore J.T., Kliewer S.A., Willson T.M., Stimmel J.B. Structural basis for antagonist-mediated recruitment of nuclear co-repressors by PPARα Nature. 415:2002;813-817.