Crystal structure of the tryparedoxin peroxidase from the human parasite Trypanosoma cruzi.
Tryparedoxin peroxidase from Trypanosoma cruzi (TcTXNPx) belongs to the family of typical 2-Cys peroxiredoxins. These enzymes function as antioxidants through their peroxidase and peroxynitrite reductase activities. In T. cruzi, as in all trypanosomatids, this enzyme is the final electron acceptor of a unique system for detoxifying hydroperoxides, constituting a relevant target for drug design. We have determined the crystal structure of TcTXPNx in the reduced active state. The structure comprises 10 subunits in the asymmetric unit, associated to form a decamer of toroidal shape obeying 52 (D5) point group symmetry. We have analyzed the structure of TcTXNPx by comparing it with other structures of typical 2-Cys peroxiredoxins in both redox states, and have identified key residues in the structural rearrangement taking place in the enzymatic cycle. This is the first report of the structure of an active peroxiredoxin that has peroxidase and peroxynitrite reductase activity, and it is noteworthy that it is from a human parasite. This knowledge is of interest for further understanding peroxide metabolism in these parasites, and in the design of new trypanosomatidal drugs against Chagas disease.
Piñeyro
María Dolores
MD
Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Avenida Gral. Flores 2125, 11800 Montevideo, Uruguay.
Pizarro
Juan Carlos
JC
Lema
Fernando
F
Pritsch
Otto
O
Cayota
Alfonso
A
Bentley
Graham A
GA
Robello
Carlos
C
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D008969:Molecular Sequence Data; D010544:Peroxidases / Q000737:chemistry*; D054464:Peroxiredoxins; D017433:Protein Structure, Secondary; D015800:Protozoan Proteins / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D014349:Trypanosoma cruzi / Q000201:enzymology*; D014961:X-Ray Diffraction
D015800:Protozoan Proteins; D011994:Recombinant Proteins; D010544:Peroxidases; C110959:tryparedoxin peroxidase; D054464:Peroxiredoxins