Design of new inhibitors specific to the adenosine triphosphate binding site of DNA topoisomerases II

Summary DNA topoisomerases II are involved in the segregation of chromosomes which occurs after DNA replication. These enzymes proceed by nicking and resealing of a phosphodiester bond of the DNA double helix and require the hydrolysis of ATP into ADP and inorganic phosphate. Studies of ATP hydrolysis showed specific properties according to the source of isolation of the enzymes, suggesting the existence of an evolution of the ATP binding site of DNA topoisomerases II. In order to study this evolution, two experimental strategies were followed, first of all an analysis of the topography of the ATP binding site by forming UV crosslinks between ATP and the enzymes, and second the effects of new inhibitors.