Structure-function relationship in a beta-sheet peptide inhibitor of E47 dimerization and DNA binding.

I Ghosh; R Issac; J Chmielewski

doi:10.1016/s0968-0896(98)00214-4

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Structure-function relationship in a beta-sheet peptide inhibitor of E47 dimerization and DNA binding.

I Ghosh·R Issac·J Chmielewski

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Abstract

A beta-sheet peptide inhibitor, 2H10, has been developed that inhibits the dimerization of the transcription factor E47. Inhibition of E47 dimerization has been demonstrated to also inhibit the DNA binding of this transcription factor. Truncated peptides based on 2H10 have demonstrated that the beta-sheet content of these peptides directly correlates with their inhibitory properties. Individual residues within 2H10 were identified that were responsible for the beta-sheet secondary structure by employing an alanine replacement strategy. The beta-sheet character of the alanine mutants also correlated well with their inhibition of E47 DNA binding. These results provide further evidence that interactions between the interfacial peptide inhibitors of E47 and the transcription factor itself are mediated by a beta-sheet structure.

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Amino Acid Sequence Circular Dichroism DNA-Binding Proteins Dimerization Models, Molecular Molecular Sequence Data Mutation Oligopeptides Peptides Protein Conformation Protein Structure, Secondary Spectroscopy, Fourier Transform Infrared Structure-Activity Relationship TCF Transcription Factors Transcription Factor 7-Like 1 Protein Transcription Factors Journal Article Research Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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I Ghosh, R Issac, J Chmielewski. 1999. Structure-function relationship in a beta-sheet peptide inhibitor of E47 dimerization and DNA binding.. https://doi.org/10.1016/s0968-0896(98)00214-4

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