Topoisomerases of kinetoplastid parasites: why so fascinating?
DNA topoisomerases are the key enzymes involved in carrying out high precision DNA transactions inside the cells. However, they are detrimental to the cell when a wide variety of topoisomerase-targeted drugs generate cytotoxic lesions by trapping the enzymes in covalent complexes on the DNA. The discovery of unusual heterodimeric topoisomerase I in kinetoplastid family added a new twist in topoisomerase research related to evolution, functional conservation and their preferential sensitivity to Camptothecin. On the other hand, structural and mechanistic studies on kinetoplastid topoisomerase II delineate some distinguishing features that differentiate the parasitic enzyme from its prokaryotic and eukaryotic counterparts. This review summarizes the recent advances in research in kinetoplastid topoisomerases, their evolutionary significance and the death of the unicellular parasite Leishmania donovani induced by topoisomerase I inhibitor camptothecin.
Das
Benu Brata
BB
Department of Molecular Parasitology, Indian Institute of Chemical Biology, Kolkata 700032, India.
Sengupta
Tanushri
T
Ganguly
Agneyo
A
Majumder
Hemanta K
HK
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology; D017209:Apoptosis; D002166:Camptothecin / Q000494:pharmacology; D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019143:Evolution, Molecular; D006801:Humans; D016830:Kinetoplastida / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
D000981:Antiprotozoal Agents; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; D002166:Camptothecin