6U4O
Crystal structure of recombinant class II fumarase from Schistosoma mansoni
Summary for 6U4O
| Entry DOI | 10.2210/pdb6u4o/pdb |
| Descriptor | Fumarate hydratase, (2S)-2-hydroxybutanedioic acid, GLYCEROL, ... (5 entities in total) |
| Functional Keywords | smfhii, fumarate hydratase, lyase |
| Biological source | Schistosoma mansoni (Blood fluke) |
| Total number of polymer chains | 4 |
| Total formula weight | 216480.52 |
| Authors | Cardoso, I.A.,Nonato, M.C. (deposition date: 2019-08-26, release date: 2020-09-02, Last modification date: 2023-10-11) |
| Primary citation | Cardoso, I.A.,de Souza, A.K.L.,Burgess, A.M.G.,Chalmers, I.W.,Hoffmann, K.F.,Nonato, M.C. Characterization of class II fumarase from Schistosoma mansoni provides the molecular basis for selective inhibition. Int.J.Biol.Macromol., 175:406-421, 2021 Cited by PubMed Abstract: Schistosomiasis is a neglected tropical disease that affects more than 250 million people worldwide. The only drug available for its treatment undergoes first-pass hepatic metabolism and is not capable of preventing reinfection, which makes the search of new therapies urgently needed. Due to the essential role of fumarases in metabolism, these enzymes represent potential targets for developing novel schistosomiasis treatments. Here, we evaluate the expression profiles for class I and class II fumarases from Schistosoma mansoni (SmFH and SmFH, respectively), and report the complete characterization of SmFH. The first SmFH structure in complex with L-malate was determined at 1.85 Å resolution. The significant thermoshift observed for SmFH in the presence of identified ligands makes the differential scanning fluorimetry an adequate technique for ligand screening. A complete kinetic characterization of SmFH was performed, and comparison with the human fumarase (HsFH) revealed differences regarding the turnover number (k). Structural characterization allowed us to identify differences between SmFH and HsFH that could be explored to design new selective inhibitors. This work represents the very first step towards validate the fumarases as drug targets to treat schistosomiasis. Our results provide the structural basis to rational search for selective ligands. PubMed: 33549669DOI: 10.1016/j.ijbiomac.2021.01.180 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.85 Å) |
Structure validation
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