Erybraedin C, a natural compound from the plant Bituminaria bituminosa, inhibits both the cleavage and religation activities of human topoisomerase I.

Cinzia Tesauro , Paola Fiorani (1) , Ilda d'Annessa , Giovanni Chillemi , Gino Turchi , Alessandro Desideri

1 Università degli Studi di Roma Tor Vergata [Roma] = University of Rome Tor Vergata

The interaction of human topoisomerase I and erybraedin C, a pterocarpan purified from the plant Bituminaria bituminosa that has been shown to have an antitumor activity, has been 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 have a complete inhibition. Molecular docking simulations indicate that, when interacting with the enzyme alone, the preferential drug binding site is localized in proximity of the active Tyr723 residue with one of the two prenilic groups close to the active site residues Arg488 and His632, 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 what found for topotecan. This is the first example of a natural compound able to act on both the cleavage and religation reaction of human topoisomerase I.

Mots clés: Life Sciences

Cinzia Tesauro, Paola Fiorani, Ilda d'Annessa, Giovanni Chillemi, Gino Turchi, et al.. Erybraedin C, a natural compound from the plant Bituminaria bituminosa, inhibits both the cleavage and religation activities of human topoisomerase I.. Biochemical Journal, 2010, 425 (3), pp.531-539. ⟨10.1042/BJ20091127⟩. ⟨hal-00479237⟩