Journal
MOLECULAR CANCER THERAPEUTICS
Volume 5, Issue 2, Pages 287-295Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1535-7163.MCT-05-0456
Keywords
-
Categories
Funding
- Intramural NIH HHS [Z99 CA999999] Funding Source: Medline
- NCI NIH HHS [U01 CA89566] Funding Source: Medline
Ask authors/readers for more resources
We show that five topoisomerase I inhibitors (two indenoisoquinolines, two camptothecins, and one indolocarbazole) each intercalate between the base pairs flanking the cleavage site generated during the topoisomerase I catalytic cycle and are further stabilized by a network of hydrogen bonds with topoisomerase I. The interfacial inhibition paradigm described for topoisomerase I inhibitors can be generalized to a variety of natural products that trap macromolecular complexes as they undergo catalytic conformational changes that create hotspots for drug binding. Stabilization of such conformational states results in uncompetitive inhibition and exemplifies the relevance of screening for ligands and drugs that stabilize (trap) these macromolecular complexes.
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