Summary information and primary citation
- PDB-id
-
3i5e;
DSSR-derived features in text and
JSON formats
- Class
- DNA
- Method
- X-ray (0.98 Å)
- Summary
- Allosteric modulation of DNA by small molecules
- Reference
-
Chenoweth DM, Dervan PB (2009): "Allosteric
modulation of DNA by small molecules."
Proc.Natl.Acad.Sci.USA, 106,
13175-13179. doi: 10.1073/pnas.0906532106.
- Abstract
- 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 A 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.
