Fumarate hydratases catalyze the stereospecific reversible hydration of fumarate to S-malate. The project aims to elucidate the mechanism of action of fumarate hydratase from Leishmania major by site directed mutagenesis, single crystal x-ray diffraction and electron paramagnetic resonance. Leishmania is a parasite that causes Leishmaniases, classified as neglected tropical deseases and threatening 350 million people around the world. Recent studies in trypanosomatids, using Trypanosoma brucei as a model, suggest that fumarate hydratase may be exploited as a potential target for the development of anti-trypanosomatid drugs. Mechanism of action studies, proposed in this work, associated to our previous kinetic, cell localization and structural studies will be used to further to establish the structure-function relationship of both fumarate hydratase enzymes in Leishmania major. The results obtained during the development of this project will provide valuable information for the development of specific inhibitors as an important tool in the fight against Leishmaniasis.
News published in Agência FAPESP Newsletter about the scholarship: