TAILIEUCHUNG - Báo cáo khoa học: A comparative study of type I and type II tryparedoxin peroxidases in Leishmania major

The genome ofLeishmania major, the causative agent of cutaneous leish-maniasis, contains three almost identical genes encoding putative glutathi-one peroxidases, which differ only at their N- and C-termini. Because the gene homologues are essential in trypanosomes, they may also represent potential drug targets inLeishmania. | ỊFEBS Journal A comparative study of type I and type II tryparedoxin peroxidases in Leishmania major Janine Konig and Alan H. Fairlamb Wellcome Trust Biocentre University of Dundee UK Keywords glutathione peroxidase Leishmania peroxiredoxin trypanothione tryparedoxin peroxidase Correspondence A. H. Fairlamb Division of Biological Chemistry Drug Discovery Wellcome Trust Biocentre College of Life Sciences University of Dundee Dundee DD1 5EH UK Fax 44 1382 385542 Tel. 44 1382 385155 E-mail Website http biocentre Received 1 August 2007 revised 3 September 2007 accepted 4 September 2007 doi The genome of Leishmania major the causative agent of cutaneous leishmaniasis contains three almost identical genes encoding putative glutathione peroxidases which differ only at their N- and C-termini. Because the gene homologues are essential in trypanosomes they may also represent potential drug targets in Leishmania. Recombinant protein for the shortest of these showed negligible peroxidase activity with glutathione as the electron donor indicating that it is not a bone fide glutathione peroxidase. By contrast high peroxidase activity was obtained with tryparedoxin indicating that these proteins belong to a new class of monomeric tryparedoxin-dependent peroxidases TDPX distinct from the classical decameric 2-Cys peroxiredoxins TryP . Mass spectrometry studies revealed that oxidation of TDPX1 with peroxides results in the formation of an intramolecular disulfide bridge between Cys35 and Cys83. Site-directed mutagenesis and kinetic studies showed that Cys35 is essential for peroxidase activity whereas Cys83 is essential for reduction by tryparedoxin. Detailed kinetic studies comparing TDPX1 and TryP1 showed that both enzymes obey saturation ping-pong kinetics with respect to tryparedoxin and peroxide. Both enzymes show high affinity for tryparedoxin and broad substrate specificity for .

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