2x8g

Oxidized thioredoxin glutathione reductase from Schistosoma mansoni

spinqualitylabelsall models 2x8g, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2x8g is a 1 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 1.9Å Ligands: FAD, GOL, PEG, PG4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q962Y6_SCHMA Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Schistosomiasis is the second most widespread human parasitic disease. It is principally treated with one drug, praziquantel that is administered to 100 million people each year; less sensitive strains of schistosomes are emerging. One of the most appealing drug targets against schistosomiasis is thioredoxin glutathione reductase (TGR). This natural chimeric enzyme is a peculiar fusion of a glutaredoxin domain with a thioredoxin Selenocysteine (Sec)-containing reductase domain. Sec is located on a flexible C-terminal arm that is usually disordered in the available structures of the protein and is essential for the full catalytic activity of TGR. In this study, we dissect the catalytic cycle of Schistosoma mansoni TGR (SmTGR) by structural and functional analysis of Sec597Cys mutant. The crystallographic data presented herein include: the oxidized form (at 1.9 A resolution); the NADPH- and GSH-bound forms (2.3 A and 1.9 A , respectively); and a different crystal form of the (partially) reduced enzyme (3.1 A ), showing the physiological dimer and the entire C-terminus of one subunit. Whenever possible, we determined the rate constants for the interconversion between the different oxidation states of TGR by kinetic methods. By combining the crystallographic analysis with computer modelling, we were able to throw further light on the mechanism of action of S. mansoni TGR. In particular, we propose hereby the putative functionally relevant conformational change of the C-terminus after the transfer of reducing equivalents from NADPH to the redox sites of the enzyme. Mapping the catalytic cycle of Schistosoma mansoni thioredoxin glutathione reductase by x-ray crystallography.,Angelucci F, Dimastrogiovanni D, Boumis G, Brunori M, Miele AE, Saccoccia F, Bellelli A J Biol Chem. 2010 Jul 21. PMID:20659890 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Thioredoxin Glutathione Reductase

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