Trypanosomatids consist of a large group of flagellated parasitic protozoa, including parasites from the genera Leishmania and
Trypanosoma, responsible for causing infections in millions of humans worldwide and for which currently no appropriate therapy is
available. The significance of pyrimidines in cellular metabolism makes their de novo and salvage pathways ideal druggable targets for
pharmacological intervention and open an opportunity for pharmaceutical innovation. In the current review, we discuss the merits in targeting
the enzyme dihydroorotate dehydrogenase (DHODH), a flavin-dependent enzyme that catalyzes the fourth and only redox step in
pyrimidine de novo biosynthesis, as a strategy for the development of efficient therapeutic strategies for trypanosomatid-related diseases.
We also describe the advances and perspectives from the structural biology point of view in order to unravel the structure-function relationship
of trypanosomatid DHODHs, and to identify and validate target sites for drug development.
Keywords: Dihydroorotate dehydrogenase, trypanosomatids, Leishmania major, Trypanosoma cruzi, Trypanosoma brucei, sites for drug
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