9Th Brazilian Symposium on Medicinal Chemistry

Schistosomiasis is second only to malaria as most devastating parasitic neglected disease in the world, and has been reported from 78 countries1; 2. The cytosolic isoform of class II fumarate hydratase of Schistosoma mansoni (SmFHII) catalyzes the reversible hydration of fumarate to L-malate and is suggested being involved in DNA repair mechanisms and urea cycle. As a first step towards evaluating SmFHII as a drug target against schistosomiasis, this project focuses on its structural and biochemical characterization. In the present work, SmFHII was successfully expressed and purified with a good yield. Kinetic assay using both substrates (L-malate and fumarate) was performed and Km values were found to be pretty similar to human fumarase. Moreover, we established a reproducible crystallization protocol, and X-ray diffraction data of recombinant SmFHII at 1.85 Å resolution allowed us to solve the first structure of S. mansoni fumarase complexed with substrate L-malate.