Two phylogenetically divergent IMP dehydrogenases in the life cycle of Trypanosoma brucei
Kanchagar, Chitra Anand
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Millions world-wide are afflicted by diseases caused by the trypanosomatids, Trypanosoma brucei, Trypanosoma cruzi and Leishmania. These parasites are unable to synthesize purines de novo; instead, they acquire pre-assembled nucleobases and nucleosides from the host through the salvage pathway. Enzymes involved in this pathway are essential for parasite viability and differ from those of the mammalian host. Therefore, they are potential drug targets. One central enzyme is IMP dehydrogenase which catalyzes the rate-limiting, penultimate step in the production of guanine nucleotides and has been described as an excellent drug target in other systems. Interestingly, two highly-divergent IMPDHs are present in the genomes of T. brucei, T. cruzi and L. donovani. One of these has been characterized in the insect stages of T. b. gambiense and L. donovani. However, the role of the second gene is unknown. In this study the role of the two IMPDHs in trypanosomatids was determined using T. brucei as a model.