Structural Mechanisms of Topoisomerase-Targeting Drugs

Topoisomerases are enzymes responsible for recognizing and resolving superhelical crossings and topological tangles in DNA. Topoisomerases also serve as valuable established targets for numerous clinically used antibacterial and antitumor agents; small-molecule antagonists not only have an ability to disrupt essential cellular functions but also convert these enzymes into DNA-damaging agents. Here, we review biochemical and structural data that explain how current therapeutics target eukaryotic and prokaryotic topoisomerases at a molecular level. New and highly promising agents that showcase the continued utility of targeting topoisomerases for clinical benefit are also discussed.