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Structural and thermodynamic consequences of the replacement of zinc with environmental metals on estrogen receptor α-DNA interactions.


ABSTRACT: Estrogen receptor α (ERα) acts as a transcription factor by virtue of the ability of its DNA-binding (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 ERα 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-binding potential, although they can compete w

SUBMITTER: Deegan BJ 

PROVIDER: S-EPMC3205435 | biostudies-literature | 2011 Nov-Dec

REPOSITORIES: biostudies-literature