Structural, biochemical and biophysical characterization of recombinant human fumarate hydratase.

Fumarate hydratases (FHs, fumarases) catalyze the reversible conversion of fumarate into l-malate. FHs are distributed over all organisms and play important roles in energy production, DNA repair and as tumor suppressors. They are very important targets both in the study of human metabolic disorders and as potential therapeutic targets in neglected tropical diseases and tuberculosis.

Structural basis for the design of selective inhibitors for Schistosoma mansoni dihydroorotate dehydrogenase.

Trematode worms of the genus Schistosoma are the causing agents of schistosomiasis, a parasitic disease responsible for a considerable economic and healthy burden worldwide. In the present work, the characterization of the enzyme dihydroorotate dehydrogenase from Schistosoma mansoni (SmDHODH) is presented. Our studies demonstrated that SmDHODH is a member of class 2 DHODHs and catalyzes the oxidation of dihydroorotate into orotate using quinone as an electron acceptor by employing a ping-pong mechanism of catalysis.

Characterisation of the fumarate hydratase repertoire in Trypanosoma cruzi.

Nifurtimox and benznidazole represent the only treatments options available targeting Chagas disease, the most important parasitic infection in the Americas. However, use of these is problematic as they are toxic and ineffective against the more severe stages of the disease. In this work, we used a multidisciplinary approach to characterise the fumarases from Trypanosoma cruzi, the causative agent of Chagas Disease.

Structural and binding studies of a C-type galactose-binding lectin from Bothrops jararacussu snake venom.

BJcuL is a snake venom galactoside-binding lectin (SVgalL) isolated from Bothrops jararacussu and is involved in a wide variety of biological activities including triggering of pro-inflammatory response, disruption of microbial biofilm structure and induction of apoptosis. In the present work, we determined the crystallographic structure of BJcuL, the first holo structure of a SVgalL, and introduced the fluorescence-based thermal stability assay (Thermofluor) as a tool for screening and characterization of the binding mechanism of SVgalL ligands. BJcuL structure revealed the existence of a porous and flexible decameric arrangement composed of disulfide-linked dimers related by a five-fold symmetry.