{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:22:55Z","timestamp":1793157775705,"version":"4.5.0"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"37","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,9,11]]},"abstract":"<jats:p>Bisphenol A (BPA) is an industrial compound and a well known endocrine-disrupting chemical with estrogenic activity. The widespread exposure of individuals to BPA is suspected to affect a variety of physiological functions, including reproduction, development, and metabolism. Here we report that the mechanisms by which BPA and two congeners, bisphenol AF and bisphenol C (BPC), bind to and activate estrogen receptors (ER) \u03b1 and \u03b2 differ from that used by 17\u03b2-estradiol. We show that bisphenols act as partial agonists of ERs by activating the N-terminal activation function 1 regardless of their effect on the C-terminal activation function 2, which ranges from weak agonism (with BPA) to antagonism (with BPC). Crystallographic analysis of the interaction between bisphenols and ERs reveals two discrete binding modes, reflecting the different activities of compounds on ERs. BPA and 17\u03b2-estradiol bind to ERs in a similar fashion, whereas, with a phenol ring pointing toward the activation helix H12, the orientation of BPC accounts for the marked antagonist character of this compound. Based on structural data, we developed a protocol for in silico evaluation of the interaction between bisphenols and ERs or other members of the nuclear hormone receptor family, such as estrogen-related receptor \u03b3 and androgen receptor, which are two known main targets of bisphenols. Overall, this study provides a wealth of tools and information that could be used for the development of BPA substitutes devoid of nuclear hormone receptor-mediated activity and more generally for environmental risk assessment.<\/jats:p>","DOI":"10.1073\/pnas.1203574109","type":"journal-article","created":{"date-parts":[[2012,8,27]],"date-time":"2012-08-27T23:18:09Z","timestamp":1346109489000},"page":"14930-14935","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":403,"title":["Structural and mechanistic insights into bisphenols action provide guidelines for risk assessment and discovery of bisphenol A substitutes"],"prefix":"10.1073","volume":"109","author":[{"given":"Vanessa","family":"Delfosse","sequence":"first","affiliation":[{"name":"Centre de Biochimie Structurale, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U1054, Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 5048, Universit\u00e9s Montpellier 1 and 2, 34090 Montpellier, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Grimaldi","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Canc\u00e9rologie de Montpellier, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U896, Centre R\u00e9gional de Lutte contre le Cancer Val d\u2019Aurelle Paul Lamarque, Universit\u00e9 Montpellier 1, 34298 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Luc","family":"Pons","sequence":"additional","affiliation":[{"name":"Centre de Biochimie Structurale, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U1054, Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 5048, Universit\u00e9s Montpellier 1 and 2, 34090 Montpellier, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelhay","family":"Boulahtouf","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Canc\u00e9rologie de Montpellier, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U896, Centre R\u00e9gional de Lutte contre le Cancer Val d\u2019Aurelle Paul Lamarque, Universit\u00e9 Montpellier 1, 34298 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albane","family":"le Maire","sequence":"additional","affiliation":[{"name":"Centre de Biochimie Structurale, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U1054, Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 5048, Universit\u00e9s Montpellier 1 and 2, 34090 Montpellier, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Cavailles","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Canc\u00e9rologie de Montpellier, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U896, Centre R\u00e9gional de Lutte contre le Cancer Val d\u2019Aurelle Paul Lamarque, Universit\u00e9 Montpellier 1, 34298 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Labesse","sequence":"additional","affiliation":[{"name":"Centre de Biochimie Structurale, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U1054, Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 5048, Universit\u00e9s Montpellier 1 and 2, 34090 Montpellier, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Bourguet","sequence":"additional","affiliation":[{"name":"Centre de Biochimie Structurale, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U1054, Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 5048, Universit\u00e9s Montpellier 1 and 2, 34090 Montpellier, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Balaguer","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Canc\u00e9rologie de Montpellier, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U896, Centre R\u00e9gional de Lutte contre le Cancer Val d\u2019Aurelle Paul Lamarque, Universit\u00e9 Montpellier 1, 34298 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,8,27]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1210\/en.2006-0561","article-title":"Exposure to environmentally relevant doses of the xenoestrogen bisphenol-A alters development of the fetal mouse mammary gland","volume":"148","author":"Vandenberg LN","year":"2007","unstructured":"LN Vandenberg, et al., Exposure to environmentally relevant doses of the xenoestrogen bisphenol-A alters development of the fetal mouse mammary gland. Endocrinology 148, 116\u2013127 (2007).","journal-title":"Endocrinology"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.taap.2007.12.008","article-title":"Human exposure to bisphenol A by biomonitoring: Methods, results and assessment of environmental exposures","volume":"228","author":"Dekant W","year":"2008","unstructured":"W Dekant, W V\u00f6lkel, Human exposure to bisphenol A by biomonitoring: Methods, results and assessment of environmental exposures. Toxicol Appl Pharmacol 228, 114\u2013134 (2008).","journal-title":"Toxicol Appl Pharmacol"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1289\/ehp.0901716","article-title":"Urinary, circulating, and tissue biomonitoring studies indicate widespread exposure to bisphenol A","volume":"118","author":"Vandenberg LN","year":"2010","unstructured":"LN Vandenberg, et al., Urinary, circulating, and tissue biomonitoring studies indicate widespread exposure to bisphenol A. Environ Health Perspect 118, 1055\u20131070 (2010).","journal-title":"Environ Health Perspect"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.chemosphere.2010.09.058","article-title":"Viable skin efficiently absorbs and metabolizes bisphenol A","volume":"82","author":"Zalko D","year":"2011","unstructured":"D Zalko, C Jacques, H Duplan, S Bruel, E Perdu, Viable skin efficiently absorbs and metabolizes bisphenol A. Chemosphere 82, 424\u2013430 (2011).","journal-title":"Chemosphere"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.reprotox.2007.05.008","article-title":"An ecological assessment of bisphenol-A: Evidence from comparative biology","volume":"24","author":"Crain DA","year":"2007","unstructured":"DA Crain, et al., An ecological assessment of bisphenol-A: Evidence from comparative biology. Reprod Toxicol 24, 225\u2013239 (2007).","journal-title":"Reprod Toxicol"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.reprotox.2007.06.004","article-title":"In vivo effects of bisphenol A in laboratory rodent studies","volume":"24","author":"Richter CA","year":"2007","unstructured":"CA Richter, et al., In vivo effects of bisphenol A in laboratory rodent studies. Reprod Toxicol 24, 199\u2013224 (2007).","journal-title":"Reprod Toxicol"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"17732","DOI":"10.1073\/pnas.1115187108","article-title":"Effects of bisphenol A and triclocarban on brain-specific expression of aromatase in early zebrafish embryos","volume":"108","author":"Chung E","year":"2011","unstructured":"E Chung, MC Genco, L Megrelis, JV Ruderman, Effects of bisphenol A and triclocarban on brain-specific expression of aromatase in early zebrafish embryos. Proc Natl Acad Sci USA 108, 17732\u201317737 (2011).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1093\/toxsci\/kfn084","article-title":"Two-generation reproductive toxicity study of dietary bisphenol A in CD-1 (Swiss) mice","volume":"104","author":"Tyl RW","year":"2008","unstructured":"RW Tyl, et al., Two-generation reproductive toxicity study of dietary bisphenol A in CD-1 (Swiss) mice. Toxicol Sci 104, 362\u2013384 (2008).","journal-title":"Toxicol Sci"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.mce.2009.02.023","article-title":"Bisphenol A: Perinatal exposure and body weight","volume":"304","author":"Rubin BS","year":"2009","unstructured":"BS Rubin, AM Soto, Bisphenol A: Perinatal exposure and body weight. Mol Cell Endocrinol 304, 55\u201362 (2009).","journal-title":"Mol Cell Endocrinol"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1289\/ehp.0800045","article-title":"Prenatal exposure to bisphenol a at environmentally relevant doses adversely affects the murine female reproductive tract later in life","volume":"117","author":"Newbold RR","year":"2009","unstructured":"RR Newbold, WN Jefferson, E Padilla-Banks, Prenatal exposure to bisphenol a at environmentally relevant doses adversely affects the murine female reproductive tract later in life. Environ Health Perspect 117, 879\u2013885 (2009).","journal-title":"Environ Health Perspect"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1289\/ehp.7713","article-title":"An extensive new literature concerning low-dose effects of bisphenol A shows the need for a new risk assessment","volume":"113","author":"vom Saal FS","year":"2005","unstructured":"FS vom Saal, C Hughes, An extensive new literature concerning low-dose effects of bisphenol A shows the need for a new risk assessment. Environ Health Perspect 113, 926\u2013933 (2005).","journal-title":"Environ Health Perspect"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1210\/er.2008-0021","article-title":"Bisphenol-A and the great divide: a review of controversies in the field of endocrine disruption","volume":"30","author":"Vandenberg LN","year":"2009","unstructured":"LN Vandenberg, MV Maffini, C Sonnenschein, BS Rubin, AM Soto, Bisphenol-A and the great divide: a review of controversies in the field of endocrine disruption. Endocr Rev 30, 75\u201395 (2009).","journal-title":"Endocr Rev"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1210\/endo.138.3.4979","article-title":"Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta","volume":"138","author":"Kuiper GG","year":"1997","unstructured":"GG Kuiper, et al., Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 138, 863\u2013870 (1997).","journal-title":"Endocrinology"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"e31109","DOI":"10.1371\/journal.pone.0031109","article-title":"Rapid insulinotropic action of low doses of bisphenol-A on mouse and human islets of Langerhans: Role of estrogen receptor \u03b2","volume":"7","author":"Soriano S","year":"2012","unstructured":"S Soriano, et al., Rapid insulinotropic action of low doses of bisphenol-A on mouse and human islets of Langerhans: Role of estrogen receptor \u03b2. PLoS ONE 7, e31109 (2012).","journal-title":"PLoS ONE"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.toxlet.2006.11.016","article-title":"Estrogens and antiestrogens activate hPXR","volume":"170","author":"Mnif W","year":"2007","unstructured":"W Mnif, et al., Estrogens and antiestrogens activate hPXR. Toxicol Lett 170, 19\u201329 (2007).","journal-title":"Toxicol Lett"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1289\/ehp.1104426","article-title":"Bisphenol A and its analogues activate human pregnane X receptor","volume":"120","author":"Sui Y","year":"2012","unstructured":"Y Sui, et al., Bisphenol A and its analogues activate human pregnane X receptor. Environ Health Perspect 120, 399\u2013405 (2012).","journal-title":"Environ Health Perspect"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1289\/ehp.10587","article-title":"Direct evidence revealing structural elements essential for the high binding ability of bisphenol A to human estrogen-related receptor-gamma","volume":"116","author":"Okada H","year":"2008","unstructured":"H Okada, et al., Direct evidence revealing structural elements essential for the high binding ability of bisphenol A to human estrogen-related receptor-gamma. Environ Health Perspect 116, 32\u201338 (2008).","journal-title":"Environ Health Perspect"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1289\/ehp.1003328","article-title":"Peroxisome proliferator-activated receptor \u03b3 is a target for halogenated analogs of bisphenol A","volume":"119","author":"Riu A","year":"2011","unstructured":"A Riu, et al., Peroxisome proliferator-activated receptor \u03b3 is a target for halogenated analogs of bisphenol A. Environ Health Perspect 119, 1227\u20131232 (2011).","journal-title":"Environ Health Perspect"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1093\/toxsci\/kfr132","article-title":"Characterization of novel ligands of ER\u03b1, Er\u03b2, and PPAR\u03b3: The case of halogenated bisphenol A and their conjugated metabolites","volume":"122","author":"Riu A","year":"2011","unstructured":"A Riu, et al., Characterization of novel ligands of ER\u03b1, Er\u03b2, and PPAR\u03b3: The case of halogenated bisphenol A and their conjugated metabolites. Toxicol Sci 122, 372\u2013382 (2011).","journal-title":"Toxicol Sci"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0303-7207(02)00094-1","article-title":"Phenylphenols, biphenols, bisphenol-A and 4-tert-octylphenol exhibit alpha and beta estrogen activities and antiandrogen activity in reporter cell lines","volume":"193","author":"Paris F","year":"2002","unstructured":"F Paris, et al., Phenylphenols, biphenols, bisphenol-A and 4-tert-octylphenol exhibit alpha and beta estrogen activities and antiandrogen activity in reporter cell lines. Mol Cell Endocrinol 193, 43\u201349 (2002).","journal-title":"Mol Cell Endocrinol"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1093\/toxsci\/kfr312","article-title":"Parallel biotransformation of tetrabromobisphenol A in Xenopus laevis and mammals: Xenopus as a model for endocrine perturbation studies","volume":"125","author":"Fini JB","year":"2012","unstructured":"JB Fini, et al., Parallel biotransformation of tetrabromobisphenol A in Xenopus laevis and mammals: Xenopus as a model for endocrine perturbation studies. Toxicol Sci 125, 359\u2013367 (2012).","journal-title":"Toxicol Sci"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"5185","DOI":"10.1210\/jc.2002-020209","article-title":"Thyroid hormone action is disrupted by bisphenol A as an antagonist","volume":"87","author":"Moriyama K","year":"2002","unstructured":"K Moriyama, et al., Thyroid hormone action is disrupted by bisphenol A as an antagonist. J Clin Endocrinol Metab 87, 5185\u20135190 (2002).","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1210\/me.2010-0284","article-title":"Minireview: Extranuclear steroid receptors: Roles in modulation of cell functions","volume":"25","author":"Levin ER","year":"2011","unstructured":"ER Levin, Minireview: Extranuclear steroid receptors: Roles in modulation of cell functions. Mol Endocrinol 25, 377\u2013384 (2011).","journal-title":"Mol Endocrinol"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1038\/nrd1551","article-title":"Principles for modulation of the nuclear receptor superfamily","volume":"3","author":"Gronemeyer H","year":"2004","unstructured":"H Gronemeyer, JA Gustafsson, V Laudet, Principles for modulation of the nuclear receptor superfamily. Nat Rev Drug Discov 3, 950\u2013964 (2004).","journal-title":"Nat Rev Drug Discov"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1152\/physrev.00026.2006","article-title":"Estrogen receptors: How do they signal and what are their targets","volume":"87","author":"Heldring N","year":"2007","unstructured":"N Heldring, et al., Estrogen receptors: How do they signal and what are their targets. Physiol Rev 87, 905\u2013931 (2007).","journal-title":"Physiol Rev"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/nrm1680","article-title":"Controlling nuclear receptors: The circular logic of cofactor cycles","volume":"6","author":"Perissi V","year":"2005","unstructured":"V Perissi, MG Rosenfeld, Controlling nuclear receptors: The circular logic of cofactor cycles. Nat Rev Mol Cell Biol 6, 542\u2013554 (2005).","journal-title":"Nat Rev Mol Cell Biol"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1093\/embo-reports\/kvd028","article-title":"Synergy between estrogen receptor alpha activation functions AF1 and AF2 mediated by transcription intermediary factor TIF2","volume":"1","author":"Benecke A","year":"2000","unstructured":"A Benecke, P Chambon, H Gronemeyer, Synergy between estrogen receptor alpha activation functions AF1 and AF2 mediated by transcription intermediary factor TIF2. EMBO Rep 1, 151\u2013157 (2000).","journal-title":"EMBO Rep"},{"key":"e_1_3_4_28_2","first-page":"1953","article-title":"Synergism between ERalpha transactivation function 1 (AF-1) and AF-2 mediated by steroid receptor coactivator protein-1: requirement for the AF-1 alpha-helical core and for a direct interaction between the N- and C-terminal domains","volume":"15","author":"M\u00e9tivier R","year":"2001","unstructured":"R M\u00e9tivier, G Penot, G Flouriot, F Pakdel, Synergism between ERalpha transactivation function 1 (AF-1) and AF-2 mediated by steroid receptor coactivator protein-1: requirement for the AF-1 alpha-helical core and for a direct interaction between the N- and C-terminal domains. Mol Endocrinol 15, 1953\u20131970 (2001).","journal-title":"Mol Endocrinol"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1016\/j.biocel.2007.01.001","article-title":"Androgen and estrogen receptors: Potential of crystallography in the fight against cancer","volume":"39","author":"Nahoum V","year":"2007","unstructured":"V Nahoum, W Bourguet, Androgen and estrogen receptors: Potential of crystallography in the fight against cancer. Int J Biochem Cell Biol 39, 1280\u20131287 (2007).","journal-title":"Int J Biochem Cell Biol"},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.beem.2005.09.002","article-title":"Lessons learnt from structural studies of the oestrogen receptor","volume":"20","author":"Pike AC","year":"2006","unstructured":"AC Pike, Lessons learnt from structural studies of the oestrogen receptor. Best Pract Res Clin Endocrinol Metab 20, 1\u201314 (2006).","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1146\/annurev-physiol-021909-135917","article-title":"Structural overview of the nuclear receptor superfamily: Insights into physiology and therapeutics","volume":"72","author":"Huang P","year":"2010","unstructured":"P Huang, V Chandra, F Rastinejad, Structural overview of the nuclear receptor superfamily: Insights into physiology and therapeutics. Annu Rev Physiol 72, 247\u2013272 (2010).","journal-title":"Annu Rev Physiol"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.taap.2008.07.017","article-title":"Profiling of benzophenone derivatives using fish and human estrogen receptor-specific in vitro bioassays","volume":"232","author":"Molina-Molina JM","year":"2008","unstructured":"JM Molina-Molina, et al., Profiling of benzophenone derivatives using fish and human estrogen receptor-specific in vitro bioassays. Toxicol Appl Pharmacol 232, 384\u2013395 (2008).","journal-title":"Toxicol Appl Pharmacol"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"17323","DOI":"10.1073\/pnas.0705356104","article-title":"Modulators of the structural dynamics of the retinoid X receptor to reveal receptor function","volume":"104","author":"Nahoum V","year":"2007","unstructured":"V Nahoum, et al., Modulators of the structural dynamics of the retinoid X receptor to reveal receptor function. Proc Natl Acad Sci USA 104, 17323\u201317328 (2007).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/nchembio.76","article-title":"NFkappaB selectivity of estrogen receptor ligands revealed by comparative crystallographic analyses","volume":"4","author":"Nettles KW","year":"2008","unstructured":"KW Nettles, et al., NFkappaB selectivity of estrogen receptor ligands revealed by comparative crystallographic analyses. Nat Chem Biol 4, 241\u2013247 (2008).","journal-title":"Nat Chem Biol"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/nchembio.451","article-title":"Coupling of receptor conformation and ligand orientation determine graded activity","volume":"6","author":"Bruning JB","year":"2010","unstructured":"JB Bruning, et al., Coupling of receptor conformation and ligand orientation determine graded activity. Nat Chem Biol 6, 837\u2013843 (2010).","journal-title":"Nat Chem Biol"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"14897","DOI":"10.1021\/bi971746l","article-title":"Altered ligand binding properties and enhanced stability of a constitutively active estrogen receptor: Evidence that an open pocket conformation is required for ligand interaction","volume":"36","author":"Carlson KE","year":"1997","unstructured":"KE Carlson, I Choi, A Gee, BS Katzenellenbogen, JA Katzenellenbogen, Altered ligand binding properties and enhanced stability of a constitutively active estrogen receptor: Evidence that an open pocket conformation is required for ligand interaction. Biochemistry 36, 14897\u201314905 (1997).","journal-title":"Biochemistry"},{"key":"e_1_3_4_37_2","first-page":"E588","article-title":"Structural basis for a molecular allosteric control mechanism of cofactor binding to nuclear receptors","volume":"109","author":"Osz J","year":"2012","unstructured":"J Osz, et al., Structural basis for a molecular allosteric control mechanism of cofactor binding to nuclear receptors. Proc Natl Acad Sci USA 109, E588\u2013E594 (2012).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.tibs.2004.04.006","article-title":"Mechanism of the nuclear receptor molecular switch","volume":"29","author":"Nagy L","year":"2004","unstructured":"L Nagy, JW Schwabe, Mechanism of the nuclear receptor molecular switch. Trends Biochem Sci 29, 317\u2013324 (2004).","journal-title":"Trends Biochem Sci"},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1210\/mend.15.3.0602","article-title":"Probing conformational changes in the estrogen receptor: Evidence for a partially unfolded intermediate facilitating ligand binding and release","volume":"15","author":"Gee AC","year":"2001","unstructured":"AC Gee, JA Katzenellenbogen, Probing conformational changes in the estrogen receptor: Evidence for a partially unfolded intermediate facilitating ligand binding and release. Mol Endocrinol 15, 421\u2013428 (2001).","journal-title":"Mol Endocrinol"},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"W485","DOI":"10.1093\/nar\/gkp368","article-title":"@TOME-2: A new pipeline for comparative modeling of protein-ligand complexes","volume":"37","author":"Pons JL","year":"2009","unstructured":"JL Pons, G Labesse, @TOME-2: A new pipeline for comparative modeling of protein-ligand complexes. Nucleic Acids Res 37, W485\u2013W491 (2009).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_41_2","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1021\/ci800298z","article-title":"Empirical scoring functions for advanced protein-ligand docking with PLANTS","volume":"49","author":"Korb O","year":"2009","unstructured":"O Korb, T St\u00fctzle, TE Exner, Empirical scoring functions for advanced protein-ligand docking with PLANTS. J Chem Inf Model 49, 84\u201396 (2009).","journal-title":"J Chem Inf Model"},{"key":"e_1_3_4_42_2","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.1021\/ci200274q","article-title":"DSX: A knowledge-based scoring function for the assessment of protein-ligand complexes","volume":"51","author":"Neudert G","year":"2011","unstructured":"G Neudert, G Klebe, DSX: A knowledge-based scoring function for the assessment of protein-ligand complexes. J Chem Inf Model 51, 2731\u20132745 (2011).","journal-title":"J Chem Inf Model"},{"key":"e_1_3_4_43_2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jsbmb.2007.06.006","article-title":"Structural determination of estrogen-related receptor gamma in the presence of phenol derivative compounds","volume":"108","author":"Abad MC","year":"2008","unstructured":"MC Abad, et al., Structural determination of estrogen-related receptor gamma in the presence of phenol derivative compounds. J Steroid Biochem Mol Biol 108, 44\u201354 (2008).","journal-title":"J Steroid Biochem Mol Biol"},{"key":"e_1_3_4_44_2","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1093\/jb\/mvm158","article-title":"Structural evidence for endocrine disruptor bisphenol A binding to human nuclear receptor ERR gamma","volume":"142","author":"Matsushima A","year":"2007","unstructured":"A Matsushima, et al., Structural evidence for endocrine disruptor bisphenol A binding to human nuclear receptor ERR gamma. J Biochem 142, 517\u2013524 (2007).","journal-title":"J Biochem"},{"key":"e_1_3_4_45_2","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.1021\/jm900096q","article-title":"Modulating retinoid X receptor with a series of (E)-3-[4-hydroxy-3-(3-alkoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)phenyl]acrylic acids and their 4-alkoxy isomers","volume":"52","author":"P\u00e9rez Sant\u00edn E","year":"2009","unstructured":"E P\u00e9rez Sant\u00edn, et al., Modulating retinoid X receptor with a series of (E)-3-[4-hydroxy-3-(3-alkoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)phenyl]acrylic acids and their 4-alkoxy isomers. J Med Chem 52, 3150\u20133158 (2009).","journal-title":"J Med Chem"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1203574109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T05:09:29Z","timestamp":1654578569000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1203574109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,8,27]]},"references-count":45,"journal-issue":{"issue":"37","published-print":{"date-parts":[[2012,9,11]]}},"alternative-id":["10.1073\/pnas.1203574109"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1203574109","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,8,27]]},"assertion":[{"value":"2012-08-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}