6u4o | pdb_00006u4o

Crystal structure of recombinant class II fumarase from Schistosoma mansoni

spinqualitylabelsall models 6u4o, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6u4o is a 4 chain structure with sequence from Schistosoma mansoni. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.85Å Ligands: ACT, GOL, LMR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A5K4ESW0_SCHMA Publication Abstract from PubMed 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 (SmFHI and SmFHII, respectively), and report the complete characterization of SmFHII. The first SmFHII structure in complex with L-malate was determined at 1.85 A resolution. The significant thermoshift observed for SmFHII in the presence of identified ligands makes the differential scanning fluorimetry an adequate technique for ligand screening. A complete kinetic characterization of SmFHII was performed, and comparison with the human fumarase (HsFH) revealed differences regarding the turnover number (kcat). Structural characterization allowed us to identify differences between SmFHII 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. Characterization of class II fumarase from Schistosoma mansoni provides the molecular basis for selective inhibition.,Cardoso IA, de Souza AKL, Burgess AMG, Chalmers IW, Hoffmann KF, Nonato MC Int J Biol Macromol. 2021 Feb 4;175:406-421. doi: 10.1016/j.ijbiomac.2021.01.180. PMID:33549669 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Fumarase

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