Better explicating the strengths and shortcomings of these models will help refine projections and improve transparency in the years ahead.
Image credit: Witsawat.S.
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Communicated by John D. Baldeschwieler, California Institute of Technology, Pasadena, CA (received for review May 23, 1997)
Abstract
Zinc finger domains are structures that mediate sequence recognition for a large number of DNA-binding proteins. These domains consist of sequences of amino acids containing cysteine and histidine residues tetrahedrally coordinated to a zinc ion. In this report, we present a means to selectively inhibit a zinc finger transcription factor with cobalt(III) Schiff-base complexes. 1H NMR spectroscopy confirmed that the structure of a zinc finger peptide is disrupted by axial ligation of the cobalt(III) complex to the nitrogen of the imidazole ring of a histidine residue. Fluorescence studies reveal that the zinc ion is displaced from the model zinc finger peptide in the presence of the cobalt complex. In addition, gel-shift and filter-binding assays reveal that cobalt complexes inhibit binding of a complete zinc finger protein, human transcription factor Sp1, to its consensus sequence. Finally, a DNA-coupled conjugate of the cobalt complexes selectively inhibited Sp1 in the presence of several other transcription factors.
Footnotes
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↵* To whom reprint requests should be addressed at: California Institute of Technology, mail code 139–74, Pasadena, CA 91125.
ABBREVIATIONS
- Co(III)-sb,
- cobalt(III) Schiff-base complex;
- COBA,
- Co(acacen)(NH3)2;
- COBI,
- Co(acacen)(imidazole)2;
- COMI,
- Co(acacen)(2-methylimidazole)2;
- COBA-acid,
- Co(aciden)(NH3)2;
- PAR,
- 4-(2-pyridylazo)resorcinol;
- acacen,
- bis(acetylacetone)ethylenediimine
- Received May 23, 1997.
- Accepted April 13, 1998.
- Copyright © 1998, The National Academy of Sciences
A cobalt complex that selectively disrupts the structure and function of zinc fingers
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