{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:50:36Z","timestamp":1791618636787,"version":"4.3.4"},"reference-count":57,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,10,3]],"date-time":"2011-10-03T00:00:00Z","timestamp":1317600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Molecular Recognition"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:p>Estrogen receptor \u03b1 (ER\u03b1) acts as a transcription factor by virtue of the ability of its DNA\u2010binding (DB) domain, comprised of a tandem pair of zinc fingers, to recognize the estrogen response element within the promoters of target genes. Herein, using an array of biophysical methods, we probe the structural consequences of the replacement of zinc within the DB domain of ER\u03b1 with various environmental metals and their effects on the thermodynamics of binding to DNA. Our data reveal that whereas the DB domain reconstituted with divalent ions of zinc, cadmium, mercury, and cobalt binds to DNA with affinities in the nanomolar range, divalent ions of barium, copper, iron, lead, manganese, nickel, and tin are unable to regenerate DB domain with DNA\u2010binding potential, although they can compete with zinc for coordinating the cysteine ligands within the zinc fingers. We also show that the metal\u2010free DB domain is a homodimer in solution and that the binding of various metals only results in subtle secondary and tertiary structural changes, implying that metal coordination may only be essential for binding to DNA. Collectively, our findings provide mechanistic insights into how environmental metals may modulate the physiological function of a key nuclear receptor involved in mediating a plethora of cellular functions central to human health and disease. Copyright \u00a9 2011 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jmr.1148","type":"journal-article","created":{"date-parts":[[2011,10,5]],"date-time":"2011-10-05T10:09:56Z","timestamp":1317809396000},"page":"1007-1017","source":"Crossref","is-referenced-by-count":26,"title":["Structural and thermodynamic consequences of the replacement of zinc with environmental metals on estrogen receptor \u03b1\u2013DNA interactions"],"prefix":"10.1002","volume":"24","author":[{"given":"Brian J.","family":"Deegan","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology and USylvester Braman Family Breast Cancer Institute, Leonard Miller School of Medicine University of Miami  Miami FL 33136 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Bona","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology and USylvester Braman Family Breast Cancer Institute, Leonard Miller School of Medicine University of Miami  Miami FL 33136 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas","family":"Bhat","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology and USylvester Braman Family Breast Cancer Institute, Leonard Miller School of Medicine University of Miami  Miami FL 33136 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Mikles","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology and USylvester Braman Family Breast Cancer Institute, Leonard Miller School of Medicine University of Miami  Miami FL 33136 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb B.","family":"McDonald","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology and USylvester Braman Family Breast Cancer Institute, Leonard Miller School of Medicine University of Miami  Miami FL 33136 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