Journal
BIOCHEMICAL JOURNAL
Volume 425, Issue -, Pages 531-539Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BJ20091127
Keywords
erybraedin C (ERYC); human topoisomerase I; inhibition mechanism; inhibitor; molecular docking; pterocarpan
Categories
Funding
- AIRC
Ask authors/readers for more resources
The interaction of human topoisomerase I and erybraedin C, a pterocarpan purified from the plant Bituminaria bituminosa, that was shown to have an antitumour activity, was investigated through enzymatic activity assays and molecular docking procedures. Erybraedin C is able to inhibit both the cleavage and the religation steps of the enzyme reaction. In both cases, preincubation of the drug with the enzyme is required to produce it complete inhibition. Molecular docking simulations indicate that, when interacting with the enzyme alone, the preferential drug-binding site is localized in proximity to the active Tyr(723) residue, with one of the two prenilic groups close to the active-site residues Arg(488) and His(632), essential for the catalytic reaction. When interacting with the cleavable complex, erybraedin C interacts with both the enzyme and DNA in a way similar to that found for topotecan. This is the first example of a natural compound able to act oil both the cleavage and religation reaction of human topoisomerase I.
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