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Structural basis for G•C recognition in the DNA minor groove

Nature Structural Biology volume 5, pages 104–109 (1998)Cite this article

Abstract

Small molecules that target specific DNA sequences offer a potentially general approach for the regulation of gene expression. Pyrrole–imidazole polyamides represent the only class of synthetic small molecules that can bind predetermined DNA sequences with affinities and specificities comparable to DNA binding proteins. Antiparallel side-by-side pairings of two aromatic amino acids, imidazole (Im) and pyrrole (Py), distinguish G·C from C·G, and both from A·T/T·A base pairs. A high resolution X-ray crystal structure of a four-ring pyrrole–imidazole polyamide specifically bound as a dimer to a six-base pair predetermined DNA site reveals a structural framework of hydrogen bonds and interactions with the walls of the minor groove that underlies the pairing rules for DNA recognition.

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Authors and Affiliations

  1. Division of Biology, California Institute of Technology,

    Clara L. Kielkopf

  2. Division of Chemistry and Chemical Engineering, California Institute of Technology,

    Eldon E. Baird, Peter B. Dervan & Douglas C. Rees

  3. The Howard Hughes Medical Institute, Pasadena, California, 91125, USA

    Douglas C. Rees

Authors
  1. Clara L. Kielkopf
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  2. Eldon E. Baird
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  3. Peter B. Dervan
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  4. Douglas C. Rees
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Kielkopf, C., Baird, E., Dervan, P. et al. Structural basis for G•C recognition in the DNA minor groove. Nat Struct Mol Biol 5, 104–109 (1998). https://doi.org/10.1038/nsb0298-104

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