Structure of Urocanate Hydratase from the protozoan Trypanosoma cruzi.
The enzyme Urocanate Hydratase (UH) participates in the catabolic pathway of L-histidine. Trypanosoma cruzi Urocanate Hydratase (TcUH) is identified as a therapeutic molecular target in the WHO/TDR Targets Database. We report the 3D structure determination and number of features of TcUH, and compared it to other few available bacterial UH structures. Each monomer presents two domains and one NAD+ molecule. Superpositions revealed differences in the relative orientation of domains within monomers, such that TcUH monomer A resembles Urocanate Hydratase from Geobacillus kaustophilus (GkUH) (open conformation), while monomer C resembles Urocanate Hydratase from Pseudomonas putida (PpUH) and Urocanate Hydratase from Bacillus subtilis (BsUH) (closed conformations). We use the structure of TcUH to make considerations about 3 non-deleterious and 2 deleterious mutations found in human UHs: non-deleterious mutations could be accommodated without large displacements or interaction interruptions, whereas deleterious mutations in one case might disrupt an α-helix (as previously suggested) and in the other case, besides disrupting the enzyme interaction with the substrate, might interfere with interdomain movement.
['Boreiko|Sheila|S|', 'Silva|Marcio|M|', 'de F P Melo|Raíssa|R|', 'Silber|Ariel M|AM|', 'Iulek|Jorge|J|']
D000595:Amino Acid Sequence D001412:Bacillus subtilis D003001:Cloning, Molecular D003460:Crystallization D056506:Geobacillus D006639:Histidine D009243:NAD D000072756:Protein Conformation, alpha-Helical D016958:Pseudomonas putida D015203:Reproducibility of Results D016415:Sequence Alignment D014349:Trypanosoma cruzi D014559:Urocanate Hydratase
Urocanate Hydratase Trypanosoma cruzi Interdomain movement Chagas disease Histidine metabolism Human Urocanate Hydratase deleterious mutations