Copper and endogenous mediators of estradiol action

Fishman, Jerry H.; Fishman, Jack

doi:10.1016/s0006-291x(88)80106-2

Cited by 11 publications

(1 citation statement)

References 7 publications

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“…It should also be noted here that the failure of DB domain regenerated with divalent ions of barium, copper, iron, lead, manganese, nickel, and tin to bind DNA does not necessarily imply failure to replace zinc within the ZFs of the DB domain. Indeed, it has been previously reported that the divalent ions of copper can replace zinc within the ZFs of DB and that such substitution is met with profound effects on the physiological action of ERα (Young et al , ; Fishman and Fishman, ; Hutchens et al , ; Predki and Sarkar, ). It is thus conceivable that divalent ions of barium, copper, iron, lead, manganese, nickel, and tin can replace zinc within the ZFs of DB domain, but their inability to coordinate cysteine ligands in a tetrahedral arrangement results in improper folding such that the DB domain can no longer recognize the target DNA.…”

Section: Resultsmentioning

confidence: 99%

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

Deegan

Bona

Bhat

et al. 2011

J of Molecular Recognition

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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 (ERE) within the promoters of target genes. Herein, using an array of biophysical methods, we probe 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 while 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 though they can compete with zinc for coordinating the cysteine ligands within the zinc fingers. We also show that the metal-free 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 DNA-binding. 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.

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Section: Resultsmentioning

confidence: 99%

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

Deegan

Bona

Bhat

et al. 2011

J of Molecular Recognition

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Clinical implications of trace elements in endocrinology

Nève

1992

Biol Trace Elem Res

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The implications of essential trace elements in endocrinological processes, mainly thyroid function, growth, gonadal function, adrenal hormones, prolactin, glucose homeostasis, calcium-phosphorus metabolism, and thymulin activity, are reviewed. Most concerned elements in this field include iodine, zinc, selenium, copper, chromium, manganese and vanadium. The minerals are powerful modulators of several physiological functions that can be considerably perturbed in deficiency states. The resulting biochemical and clinical modifications can be prevented and/or corrected by adequate supplementation. Sometimes, however, they act like pharmacological agents when their beneficial effects are not the result of a correction of a nutritional deficiency state. Their potentialities as therapeutic agents are perfectly described in many cases, but some indications deserve further investigations.

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Occupancy of a C₂‐C₂ type ‘Zinc‐finger’ protein domain by copper Direct observation by electrospray ionization mass spectrometry

Hutchens

Allen

et al. 1992

FEBS Letters

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Copper and endogenous mediators of estradiol action

Cited by 11 publications

References 7 publications

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

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

Clinical implications of trace elements in endocrinology

Occupancy of a C₂‐C₂ type ‘Zinc‐finger’ protein domain by copper Direct observation by electrospray ionization mass spectrometry

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Copper and endogenous mediators of estradiol action

Cited by 11 publications

References 7 publications

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

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

Clinical implications of trace elements in endocrinology

Occupancy of a C2‐C2 type ‘Zinc‐finger’ protein domain by copper Direct observation by electrospray ionization mass spectrometry

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Occupancy of a C₂‐C₂ type ‘Zinc‐finger’ protein domain by copper Direct observation by electrospray ionization mass spectrometry