{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T15:53:20Z","timestamp":1793116400046,"version":"4.5.0"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,5,26]]},"abstract":"<jats:p>The 2.8-\u212b crystal structure of the complex formed by estradiol and the human estrogen receptor-\u03b1 ligand binding domain (hER\u03b1LBD) is described and compared with the recently reported structure of the progesterone complex of the human progesterone receptor ligand binding domain, as well as with similar structures of steroid\/nuclear receptor LBDs solved elsewhere. The hormone-bound hER\u03b1LBD forms a distinctly different and probably more physiologically important dimer interface than its progesterone counterpart. A comparison of the specificity determinants of hormone binding reveals a common structural theme of mutually supported van der Waals and hydrogen-bonded interactions involving highly conserved residues. The previously suggested mechanism by which the estrogen receptor distinguishes estradiol\u2019s unique 3-hydroxy group from the 3-keto function of most other steroids is now described in atomic detail. Mapping of mutagenesis results points to a coactivator-binding surface that includes the region around the \u201csignature sequence\u201d as well as helix 12, where the ligand-dependent conformation of the activation function 2 core is similar in all previously solved steroid\/nuclear receptor LBDs. A peculiar crystal packing event displaces helix 12 in the hER\u03b1LBD reported here, suggesting a higher degree of dynamic variability than expected for this critical substructure.<\/jats:p>","DOI":"10.1073\/pnas.95.11.5998","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:40:11Z","timestamp":1027680011000},"page":"5998-6003","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":626,"title":["Crystallographic comparison of the estrogen and progesterone receptor\u2019s ligand binding domains"],"prefix":"10.1073","volume":"95","author":[{"given":"David M.","family":"Tanenbaum","sequence":"first","affiliation":[{"name":"Department of Molecular Biophysics and Biochemistry and the Howard Hughes Medical Institute, Yale University, 260 Whitney Avenue, JWG 423, New Haven, CT 06511"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics and Biochemistry and the Howard Hughes Medical Institute, Yale University, 260 Whitney Avenue, JWG 423, New Haven, CT 06511"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn P.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics and Biochemistry and the Howard Hughes Medical Institute, Yale University, 260 Whitney Avenue, JWG 423, New Haven, CT 06511"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B.","family":"Sigler","sequence":"additional","affiliation":[{"name":"Department of Molecular Biophysics and Biochemistry and the Howard Hughes Medical Institute, Yale University, 260 Whitney Avenue, JWG 423, New Haven, CT 06511"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1998,5,26]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/39645","volume":"389","author":"Brzozowski A M","year":"1997","unstructured":"A M Brzozowski, A C W Pike, Z Dauter, R E Hubbard, T Bonn, O Engstr\u00f6m, L \u00d6hman, G L Greene, J Gustafsson, M Carlquist Nature (London) 389, 753\u2013758 (1997).","journal-title":"Nature (London)"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nsb0196-87","volume":"3","author":"Wurtz J M","year":"1996","unstructured":"J M Wurtz, W Bourguet, J P Renaud, V Vivat, P Chambon, D Moras, H Gronemeyer Nat Struct Biol 3, 87\u201394 (1996).","journal-title":"Nat Struct Biol"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/0092-8674(95)90199-X","volume":"83","author":"Mangelsdorf D J","year":"1995","unstructured":"D J Mangelsdorf, C Thummel, M Beato, P Herrlich, G Sch\u00fctz, K Umesono, B Blumberg, P Kastner, M Mark, P Chambon, R M Evans Cell 83, 835\u2013839 (1995).","journal-title":"Cell"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S1074-5521(96)90143-X","volume":"3","author":"Katzenellenbogen J A","year":"1996","unstructured":"J A Katzenellenbogen, B S Katzenellenbogen Chem Biol 3, 529\u2013536 (1996).","journal-title":"Chem Biol"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"12062","DOI":"10.1074\/jbc.272.18.12062","volume":"272","author":"Th\u00e9not S","year":"1997","unstructured":"S Th\u00e9not, C Henriquet, H Rochefort, V Cavaill\u00e8s J Biol Chem 272, 12062\u201312068 (1997).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/377454a0","volume":"377","author":"Chen J D","year":"1995","unstructured":"J D Chen, R M Evans Nature (London) 377, 454\u2013457 (1995).","journal-title":"Nature (London)"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/377397a0","volume":"377","author":"Horlein A J","year":"1995","unstructured":"A J Horlein, A M Naar, T Heinzel, J Torchia, B Gloss, R Kurokawa, A Ryan, Y Kamei, M Soderstrom, C K Glass, M G Rosenfeld Nature (London) 377, 397\u2013404 (1995).","journal-title":"Nature (London)"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1210\/mend.11.6.0009","volume":"11","author":"Smith C L","year":"1997","unstructured":"C L Smith, Z Nawaz, B W O\u2019Malley Mol Endocrinol 11, 657\u2013666 (1997).","journal-title":"Mol Endocrinol"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1210\/mend.11.7.9939","volume":"11","author":"El-Tanani M K K","year":"1997","unstructured":"M K K El-Tanani, C D Green Mol Endocrinol 11, 928\u2013937 (1997).","journal-title":"Mol Endocrinol"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1002\/j.1460-2075.1996.tb00471.x","volume":"15","author":"Migliaccio A","year":"1996","unstructured":"A Migliaccio, M Di Domenico, G Castoria, A de Falco, P Bontempo, E Nola, F Auricchio EMBO J 15, 1292\u20131300 (1996).","journal-title":"EMBO J"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/0092-8674(95)90201-5","volume":"83","author":"Beato M","year":"1995","unstructured":"M Beato, P Herrlich, G Schutz Cell 83, 851\u2013857 (1995).","journal-title":"Cell"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1126\/science.277.5331.1508","volume":"277","author":"Paech K","year":"1997","unstructured":"K Paech, P Webb, G G Kuiper, S Nilsson, J Gustafsson, P J Kushner, T S Scanlan Science 277, 1508\u20131510 (1997).","journal-title":"Science"},{"key":"e_1_3_4_13_2","first-page":"5940","volume":"53","author":"Roman S D","year":"1993","unstructured":"S D Roman, C J Ormandy, D L Manning, R W Blamey, R I Nicholson, R L Sutherland, C L Clarke Cancer Res 53, 5940\u20135945 (1993).","journal-title":"Cancer Res"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1210\/endo-122-3-935","volume":"122","author":"Nardulli A M","year":"1988","unstructured":"A M Nardulli, G L Greene, B W O\u2019Malley, B S Katzenellenbogen Endocrinology 122, 935\u2013944 (1988).","journal-title":"Endocrinology"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/378681a0","volume":"378","author":"Renaud J P","year":"1995","unstructured":"J P Renaud, N Rochel, M Ruff, V Vivat, P Chambon, H Gronemeyer, D Moras Nature (London) 378, 681\u2013689 (1995).","journal-title":"Nature (London)"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/378690a0","volume":"378","author":"Wagner R L","year":"1995","unstructured":"R L Wagner, J W Apriletti, M E McGrath, B L West, J D Baxter, R J Fletterick Nature (London) 378, 690\u2013697 (1995).","journal-title":"Nature (London)"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/375377a0","volume":"375","author":"Bourguet W","year":"1995","unstructured":"W Bourguet, M Ruff, P Chambon, H Gronemeyer, D Moras Nature (London) 375, 377\u2013382 (1995).","journal-title":"Nature (London)"},{"key":"e_1_3_4_18_2","unstructured":"Williams S. P. & Sigler P. B. (1998) Nature (London) in press."},{"key":"e_1_3_4_19_2","first-page":"647","volume":"9","author":"Seielstad D A","year":"1995","unstructured":"D A Seielstad, K E Carlson, J A Katzenellenbogen, P J Kushner, G L Greene Mol Endocrinol 9, 647\u2013648 (1995).","journal-title":"Mol Endocrinol"},{"key":"e_1_3_4_20_2","first-page":"56","volume-title":"Data Collection and Processing","author":"Otwinowski Z","year":"1993","unstructured":"Z Otwinowski Data Collection and Processing, eds L Sawyer, N Isaacs, S W Baily (Science and Engineering Council\/Daresbury Laboratory, Warrington, U.K.), pp. 56\u201362 (1993)."},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1107\/S0907444994003112","volume":"50","year":"1994","unstructured":"Acta Crystallogr D 50, 760\u2013763 (1994).","journal-title":"Acta Crystallogr D"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1107\/S0907444995008754","volume":"52","author":"Abahams J P","year":"1996","unstructured":"J P Abahams, A G W Leslie Acta Crystallogr D 52, 30\u201342 (1996).","journal-title":"Acta Crystallogr D"},{"key":"e_1_3_4_23_2","first-page":"59","volume-title":"From First Map to Final Model (CCP4)","author":"Kleywegt G T","year":"1994","unstructured":"G T Kleywegt, T A Jones From First Map to Final Model (CCP4), eds S Baily, R Hubbard, D Waller (Science and Engineering Council\/Daresbury Laboratory, Warrington, U.K.), pp. 59\u201366 (1994)."},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1107\/S0108767390010224","volume":"42","author":"Jones T A","year":"1991","unstructured":"T A Jones, J Y Zou, S W Cowan, M Kjeldgaard Acta Crystallogr A 42, 110\u2013119 (1991).","journal-title":"Acta Crystallogr A"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"5018","DOI":"10.1073\/pnas.94.10.5018","volume":"94","author":"Adams P D","year":"1997","unstructured":"P D Adams, N S Pannu, R J Read, A T Brunger Proc Natl Acad Sci USA 94, 5018\u20135023 (1997).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/0092-8674(88)90017-7","volume":"55","author":"Kumar V","year":"1988","unstructured":"V Kumar, P Chambon Cell 55, 145\u2013156 (1988).","journal-title":"Cell"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/0092-8674(93)90390-C","volume":"75","author":"Schwabe J W","year":"1993","unstructured":"J W Schwabe, L Chapman, J T Finch, D Rhodes Cell 75, 567\u2013578 (1993).","journal-title":"Cell"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/0092-8674(90)90343-D","volume":"60","author":"Fawell S E","year":"1990","unstructured":"S E Fawell, J A Lees, R White, M G Parker Cell 60, 953\u2013962 (1990).","journal-title":"Cell"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1107\/S0021889891007240","volume":"24","author":"Carlson M","year":"1991","unstructured":"M Carlson J Appl Crystallogr A 24, 958\u2013961 (1991).","journal-title":"J Appl Crystallogr A"},{"key":"e_1_3_4_30_2","first-page":"5529","volume":"10","author":"Lees J A","year":"1990","unstructured":"J A Lees, S E Fawell, R White, M G Parker Mol Cell Biol 10, 5529\u20135531 (1990).","journal-title":"Mol Cell Biol"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0092-8674(95)90307-0","volume":"82","author":"Yang W","year":"1995","unstructured":"W Yang, T A Steitz Cell 82, 193\u2013207 (1995).","journal-title":"Cell"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1210\/mend-3-10-1610","volume":"3","author":"Forman B M","year":"1989","unstructured":"B M Forman, C R Yang, M Au, J Casanova, J Ghysdael, H H Samuels Mol Endocrinol 3, 1610\u20131626 (1989).","journal-title":"Mol Endocrinol"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1093\/nar\/23.4.606","volume":"23","author":"Nishikawa J","year":"1995","unstructured":"J Nishikawa, M Kitaura, M Imagawa, T Nishihara Nucleic Acids Res 23, 606\u2013611 (1995).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1002\/j.1460-2075.1995.tb07194.x","volume":"14","author":"LeDouarin B","year":"1995","unstructured":"B LeDouarin, C Zechel, J M Garnier, Y Lutz, L Tora, P Pierrat, D Heery, H Gronemeyer, P Chambon, R Losson EMBO J 14, 2020\u20132033 (1995).","journal-title":"EMBO J"},{"key":"e_1_3_4_35_2","first-page":"958","volume":"10","author":"Perlmann T","year":"1996","unstructured":"T Perlmann, K Umesono, P N Rangarajan, B M Forman, R Evans Mol Endocrinol 10, 958\u2013966 (1996).","journal-title":"Mol Endocrinol"},{"key":"e_1_3_4_36_2","volume-title":"midasplus","year":"1989","unstructured":"midasplus (Univ. of California, San Francisco, 1989)."},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1107\/S0108767386099622","volume":"42","author":"Reed R J","year":"1986","unstructured":"R J Reed Acta Crystallogr A 42, 140\u2013149 (1986).","journal-title":"Acta Crystallogr A"},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/0263-7855(93)87009-T","volume":"11","author":"Evans S V","year":"1993","unstructured":"S V Evans J Mol Graphics 11, 134\u2013138 (1993).","journal-title":"J Mol Graphics"},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/S0955-0674(97)80066-X","volume":"9","author":"Glass C K","year":"1997","unstructured":"C K Glass, D W Rose, M G Rosenfeld Curr Opin Cell Biol 9, 222\u2013232 (1997).","journal-title":"Curr Opin Cell Biol"},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1002\/j.1460-2075.1992.tb05141.x","volume":"11","author":"Danielian P S","year":"1992","unstructured":"P S Danielian, R White, J A Lees, M G Parker EMBO J 11, 1025\u20131033 (1992).","journal-title":"EMBO J"},{"key":"e_1_3_4_41_2","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1128\/MCB.17.4.1832","volume":"17","author":"Henittu P M A","year":"1997","unstructured":"P M A Henittu, E Kalkhoven, M G Parker Mol Cell Biol 17, 1832\u20131839 (1997).","journal-title":"Mol Cell Biol"},{"key":"e_1_3_4_42_2","first-page":"1519","volume":"10","author":"McInerney E M","year":"1996","unstructured":"E M McInerney, B A Ince, D J Shapiro, B S Katzenellenbogen Mol Endocrinol 10, 1519\u20131526 (1996).","journal-title":"Mol Endocrinol"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.95.11.5998","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T21:27:05Z","timestamp":1654550825000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.95.11.5998"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,5,26]]},"references-count":42,"journal-issue":{"issue":"11","published-print":{"date-parts":[[1998,5,26]]}},"alternative-id":["10.1073\/pnas.95.11.5998"],"URL":"https:\/\/doi.org\/10.1073\/pnas.95.11.5998","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,5,26]]},"assertion":[{"value":"1998-02-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1998-05-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}