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

Louie, A. Y. and Meade, T. J. (1998) A cobalt complex that selectively disrupts the structure and function of zinc fingers. Proceedings of the National Academy of Sciences of the United States of America, 95 (12). pp. 6663-6668. ISSN 0027-8424. PMCID PMC22591. http://resolver.caltech.edu/CaltechAUTHORS:20141125-151941705

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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. ^(1)H 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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.95.12.6663DOIArticle
http://www.pnas.org/content/95/12/6663PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC22591/PubMed CentralArticle
Additional Information:© 1998 The National Academy of Sciences. Communicated by John D. Baldeschwieler, California Institute of Technology, Pasadena, CA, April 13, 1998 (received for review May 23, 1997). We thank Drs. Keiko Kato, Scott Fraser, and Harry Gray for helpful discussion and Bassil Dahiyat for assistance with the CD measurements. This work was supported by the Biological Imaging Center of the Beckman Institute and the Redox Pharmaceutical Corporation. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked ‘‘advertisement’’ in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Funders:
Funding AgencyGrant Number
Caltech Beckman InstituteUNSPECIFIED
Redox Pharmaceutical CorporationUNSPECIFIED
Subject Keywords:zinc fingers; transition metals; Sp1; nucleocapsid protein; HIV
PubMed Central ID:PMC22591
Record Number:CaltechAUTHORS:20141125-151941705
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20141125-151941705
Official Citation:Louie, A. Y., & Meade, T. J. (1998). A cobalt complex that selectively disrupts the structure and function of zinc fingers. Proceedings of the National Academy of Sciences, 95(12), 6663-6668.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52165
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:26 Nov 2014 15:31
Last Modified:20 Jul 2017 19:24

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