DNA topoisomerases in the unicellular protozoan parasites: Unwinding the mystery.

DNA topoisomerases are a group of enzymes present ubiquitously in all organisms from unicellular protozoan parasites to humans. These enzymes control the topological problems caused by DNA double helix in the cell during nucleic acid metabolism. Certain types of topoisomerases present in unicellular parasites are quite different from human topoisomerases (hTop) concerning structure, expression, and function. Many protozoan parasites causing fatal diseases have DNA topoisomerases, which play vital roles in their survival. Given the fact that the structures of the protozoan parasite topoisomerases are different from humans, DNA topoisomerase acts as an essential target for potent drug development for parasitic diseases. Moreover, various studies revealed the therapeutic potential of these drugs targeting the parasitic topoisomerases. Therefore, the characterization of parasitic topoisomerases is pivotal for the development of future potential drug targets. Considering the importance of this ubiquitous enzyme as a potential drug target, we describe in detail all the reported protozoan topoisomerases in an organized manner including Leishmania, Trypanosoma, Plasmodium, Giardia, Entamoeba, Babesia, Theileria, Crithidia, Cryptosporidium, Toxoplasma, etc. This review highlights the unique attributes associated with the structure and function of different types of DNA topoisomerases from the unicellular protozoan parasites. So, it would be beneficial for researchers to obtain awareness about the currently characterized topoisomerases and the ones that need better characterization, understand the structure-function relationship of parasitic topoisomerases, to develop the potent anti-parasitic drugs, and also provides a future platform for therapeutic development.