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Only glycine\u2014not methionine or leucine\u2014at position 575 allowed binding of RU486 to cPR. Substitution of this glycine by cysteine in the human PR (hPR) abrogated binding of RU486 but not that of an agonist. The corresponding mutation in the human glucocorticoid receptor resulted in a loss of binding of both dexamethasone and RU486. Examination of a series of 11\u03b2-substituted steroids showed that antagonism is not an intrinsic property of an antihormone, because one hPR antagonist acted as an agonist for a mutated hPR. The positioning of an aromatic 11\u03b2-substitution in the PR HBD appears to be critical for generating agonistic or antagonistic activity.<\/jats:p>","DOI":"10.1126\/science.1372753","type":"journal-article","created":{"date-parts":[[2006,10,5]],"date-time":"2006-10-05T23:03:06Z","timestamp":1160089386000},"page":"206-209","source":"Crossref","is-referenced-by-count":111,"title":["A Single Amino Acid That Determines the Sensitivity of Progesterone Receptors to RU486"],"prefix":"10.1126","volume":"255","author":[{"given":"Brigitte","family":"Benhamou","sequence":"first","affiliation":[{"name":"Roussel-Ucaf, Recherche Sant\u00e9, Departement Endocrnologie, Centre de Recherche Roussel-Uclaf, 93230 Romainville, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Garcia","sequence":"additional","affiliation":[{"name":"Roussel-Ucaf, Recherche Sant\u00e9, Departement Endocrnologie, Centre de Recherche Roussel-Uclaf, 93230 Romainville, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Lerouge","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire des Eucaryotes du CNRS, Unite 184 de Biologic Mol\u00e9culaire et de G\u00e9nie G\u00e9n\u00e9tique de I'INSERM, Institut de Chimie Biologique, Facult\u00e9 de M\u00e9decine, 67085 Strasbourg-Cedex, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnes","family":"Vergezac","sequence":"additional","affiliation":[{"name":"Roussel-Ucaf, Recherche Sant\u00e9, Departement Endocrnologie, Centre de Recherche Roussel-Uclaf, 93230 Romainville, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Gofflo","sequence":"additional","affiliation":[{"name":"Roussel-Ucaf, Recherche Sant\u00e9, Departement Endocrnologie, Centre de Recherche Roussel-Uclaf, 93230 Romainville, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Bigogne","sequence":"additional","affiliation":[{"name":"Roussel-Ucaf, Recherche Sant\u00e9, Departement Endocrnologie, Centre de Recherche Roussel-Uclaf, 93230 Romainville, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Chambon","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire des Eucaryotes du CNRS, Unite 184 de Biologic Mol\u00e9culaire et de G\u00e9nie G\u00e9n\u00e9tique de I'INSERM, Institut de Chimie Biologique, Facult\u00e9 de M\u00e9decine, 67085 Strasbourg-Cedex, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hinrich","family":"Gronemeyer","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Mol\u00e9culaire des Eucaryotes du CNRS, Unite 184 de Biologic Mol\u00e9culaire et de G\u00e9nie G\u00e9n\u00e9tique de I'INSERM, Institut de Chimie Biologique, Facult\u00e9 de M\u00e9decine, 67085 Strasbourg-Cedex, France."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_2_1_1_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3037703"},{"key":"e_1_2_1_2_1","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/345547a0","volume":"345","year":"1990","unstructured":"Bagchi, M. 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