Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 32, Pages 13175-13179Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0906532106
Keywords
DNA binders; gene regulation; minor groove binders; Py-Im polyamides; crystal structure
Categories
Funding
- U. S. Department of Energy and the National Institutes of Health
- Gordon and Betty Moore Foundation
- National Institutes of Health
- Kanel Foundation
Ask authors/readers for more resources
Many human diseases are caused by dysregulated gene expression. The oversupply of transcription factors may be required for the growth and metastatic behavior of human cancers. Cell permeable small molecules that can be programmed to disrupt transcription factor-DNA interfaces could silence aberrant gene expression pathways. Pyrrole-imidazole polyamides are DNA minor-groove binding molecules that are programmable for a large repertoire of DNA motifs. A high resolution X-ray crystal structure of an 8-ring cyclic Py/Im polyamide bound to the central 6 bp of the sequence d(5'-CCAGGCCTGG-3') 2 reveals a 4 angstrom widening of the minor groove and compression of the major groove along with a > 18 degrees bend in the helix axis toward the major groove. This allosteric perturbation of the DNA helix provides a molecular basis for disruption of transcription factor-DNA interfaces by small molecules, a minimum step in chemical control of gene networks.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available