Estudos estruturais das enzimas urocanato hidratase de Trypanosoma cruzi, gliceraldeído-3-fosfato desidrogenase de Schistosoma mansoni e glicose -6-fosfato-1-empimerase de Naegleria gruberi

Abstract

Structural studies of enzymes that participate in the metabolic pathways of pathogenic organisms or their congeners can serve as a basis for planning inhibitors. In this context, this work unveils the three-dimensional structures of three enzymes: Urocanate Hydratase from Trypanosoma cruzi, Glyceraldehyde-3-Phosphate Dehydrogenase from Schistosoma mansoni and Glucose-6-Phosphate-1-Epimerase from Naegleria gruberi. Urocanate Hydratase participates in the L-histidine metabolic pathway; it was crystallized and had its structure solved at 2.16 Å resolution, which was deposited in the PBD under code 6UEK. Structural comparisons indicated differences in the conformation of monomers A and C, which were explored to understand structural changes in the catalysis; we also use the structure to make considerations about natural mutations found in the corresponding human enzymes. Glyceraldehyde-3-Phosphate Dehydrogenase participates in the glycolytic pathway and had its structure solved at 2.51 Å of resolution, which was deposited in the PDB under code 7JH0. This is the only GAPDH that has the NNR sequence (114-116), which leads to (especially R116) a network of hydrogen bonds that possibly reflects on the flexibility of the residues to interact with the NAD+ adenine ring, residues that are speculated to be important for the differential design of inhibitors. Glucose-6-Phosphate-1-Epimerase, also part of the glycolytic pathway, had its structure modeled by homology due to the impossibility of obtaining crystals of good quality.