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Structural Basis for G•C Recognition in the DNA Minor Groove

Kielkopf, Clara L. and Baird, Eldon E. and Dervan, Peter B. and Rees, Douglas C. (1998) Structural Basis for G•C Recognition in the DNA Minor Groove. Nature Structural Biology, 5 (2). pp. 104-109. ISSN 1072-8368. doi:10.1038/nsb0298-104.

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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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URLURL TypeDescription DOIArticle
Dervan, Peter B.0000-0001-8852-7306
Rees, Douglas C.0000-0003-4073-1185
Additional Information:© 1998 Nature Publishing Group. Received 3 November, 1997; accepted 30 December, 1997. We are grateful to the NIH for research support, the NSF for a predoctoral fellowship to C.L.K., and the HHMI for a predoctoral fellowship to E.E.B. We thank JE. Wedekind, H. Schindelin, C. Kisker, L. Joshua-Tor, PM. Takahara and the members of the Rees group for guidance during the structure determination. The rotation camera facility at SSRL is supported by the Department of Energy and NIH.
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Deposited On:09 Jan 2015 19:04
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