Structural Basis for G•C Recognition in the DNA Minor Groove
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.
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.Additional details
- Eprint ID
- 53430
- DOI
- 10.1038/nsb0298-104
- Resolver ID
- CaltechAUTHORS:20150108-160953214
- NIH
- NSF
- Howard Hughes Medical Institute (HHMI)
- Department of Energy (DOE)
- Created
-
2015-01-09Created from EPrint's datestamp field
- Updated
-
2021-11-10Created from EPrint's last_modified field