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.
Keywords: cancer; infectious disease; protein–drug interactions; topoisomerase.