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THE STRUCTURE OF TRYPANOSOMA CRUZI TRYPANOTHIONE REDUCTASE IN THE OXIDIZED AND NADPH REDUCED STATETHE STRUCTURE OF TRYPANOSOMA CRUZI TRYPANOTHIONE REDUCTASE IN THE OXIDIZED AND NADPH REDUCED STATE
Structural highlights
FunctionTYTR_TRYCR Trypanothione is the parasite analog of glutathione; this enzyme is the equivalent of glutathione reductase. 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 PubMedThe three-dimensional structure of trypanothione reductase (TR) (EC 1.6.4.8) from Trypanosoma cruzi has been solved at 0.33 nm resolution by molecular replacement using the structure of C. fasciculata TR as a starting model. Elucidation of the T. cruzi TR structure represents the first step in the rational design of a drug against Chagas' disease. The structure of T. cruzi TR is compared with those of C. fasciculata TR as well as human and E. coli glutathione reductase (GR). In the FAD-binding domain, TR has two insertions, each about 10 residues long, which do not occur in GR. The first one is a rigid loop stabilizing the position of helix 91-117 which is responsible for the wider active site of TR as compared to GR. The second insertion does not occur where it is predicted by sequence alignment; rather the residues extend three strands of the 4-stranded beta-sheet by one or two residues each. This increases the number of hydrogen bonds within the sheet structure. The structure of the NADPH.TR complex has been solved at 0.33 nm resolution. The nicotinamide ring is sandwiched between the flavin ring and the side chain of Phe-198 which undergoes the same conformational change upon coenzyme binding as Tyr-197 in GR. In addition to Arg-222 and Arg-228, which are conserved in TR and GR, Tyr-221--the last residue of the second beta-sheet strand of the beta alpha beta dinucleotide binding fold--is in hydrogen bonding distance to the 2' phosphate group of NADPH. The structure of Trypanosoma cruzi trypanothione reductase in the oxidized and NADPH reduced state.,Lantwin CB, Schlichting I, Kabsch W, Pai EF, Krauth-Siegel RL Proteins. 1994 Feb;18(2):161-73. PMID:8159665[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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