A cobalt complex that selectively disrupts the structure and function of zinc fingers

A. Y. Louie, T. J. Meade

Research output: Contribution to journalArticle

65 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)6663-6668
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number12
DOIs
StatePublished - Jun 9 1998
Externally publishedYes

Fingerprint

Zinc Fingers
Cobalt
Histidine
Zinc
Transcription Factors
Ions
Peptides
Schiff Bases
Consensus Sequence
DNA-Binding Proteins
Cysteine
Ligation
Amino Acid Sequence
Magnetic Resonance Spectroscopy
Nitrogen
Fluorescence
Gels
DNA
Proteins

Keywords

  • HIV
  • Nucleocapsid protein
  • Sp1
  • Transition metals
  • Zinc fingers

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

A cobalt complex that selectively disrupts the structure and function of zinc fingers. / Louie, A. Y.; Meade, T. J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 12, 09.06.1998, p. 6663-6668.

Research output: Contribution to journalArticle

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