Structural basis for GC recognition in the DNA minor groove

• Published in: Nature structural biology Vol. 5; no. 2; pp. 104 - 109
• Main Authors: Kielkopf, Clara L, Baird, Eldon E, Dervan, Peter B, Rees, Douglas C
• Format: Journal Article
• Language: English
• Published: United States 01-02-1998
• Subjects: Base Composition; Crystallography, X-Ray; Deoxyribonucleotides - chemical synthesis; Deoxyribonucleotides - chemistry; Dimerization; DNA - chemistry; Hydrogen Bonding; Imidazoles - chemistry; Nucleic Acid Conformation; Pyrroles - chemistry
• DOI: 10.1038/nsb0298-104
• EISSN: 2331-365X
• ISSN: 1072-8368

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.