TcGPXII, a glutathione-dependent Trypanosoma cruzi peroxidase with substrate specificity restricted to fatty acid and phospholipid hydroperoxides, is localized to the endoplasmic reticulum


Wilkinson, SR; Taylor, MC; Touitha, S; Mauricio, IL; Meyer, DJ; Kelly, JM; (2002) TcGPXII, a glutathione-dependent Trypanosoma cruzi peroxidase with substrate specificity restricted to fatty acid and phospholipid hydroperoxides, is localized to the endoplasmic reticulum. The Biochemical journal, 364 (Pt 3). pp. 787-94. ISSN 0264-6021 DOI: https://doi.org/10.1042/BJ20020038

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Abstract

Until recently, it had been thought that trypanosomes lack glutathione peroxidase activity. Here we report the subcellular localization and biochemical properties of a second glutathione-dependent peroxidase from Trypanosoma cruzi (TcGPXII). TcGPXII is a single-copy gene which encodes a 16 kDa protein that appears to be specifically dependent on glutathione as the source of reducing equivalents. Recombinant TcGPXII was purified and shown to have peroxidase activity towards a narrow substrate range, restricted to hydroperoxides of fatty acids and phospholipids. Analysis of the pathway revealed that TcGPXII activity could be readily saturated by glutathione and that the peroxidase functioned by a Ping Pong mechanism. Enzyme reduction was shown to be the rate-limiting step in this pathway. Using immunofluorescence, TcGPXII was shown to co-localize with a homologue of immunoglobulin heavy-chain binding protein (BiP), a protein restricted to the endoplasmic reticulum and Golgi. As the smooth endoplasmic reticulum is the site of phospholipid and fatty acid biosynthesis, this suggests that TcGPXII may play a specific role in the T. cruzi oxidative defence system by protecting newly synthesized lipids from peroxidation.

Item Type: Article
Keywords: Amino Acid Sequence, Animal, Fatty Acids/*metabolism, Glutathione/metabolism, Glutathione Peroxidase/chemistry/genetics/*metabolism, Human, Hydrogen Peroxide/*metabolism, Kinetics, Molecular Sequence Data, Phospholipids/*metabolism, Phylogeny, Recombinant Proteins/metabolism, Sequence Alignment, Sequence Homology, Amino Acid, Substrate Specificity, Support, Non-U.S. Gov't, Trypanosoma cruzi/*enzymology, Amino Acid Sequence, Animal, Fatty Acids, metabolism, Glutathione, metabolism, Glutathione Peroxidase, chemistry, genetics, metabolism, Human, Hydrogen Peroxide, metabolism, Kinetics, Molecular Sequence Data, Phospholipids, metabolism, Phylogeny, Recombinant Proteins, metabolism, Sequence Alignment, Sequence Homology, Amino Acid, Substrate Specificity, Support, Non-U.S. Gov't, Trypanosoma cruzi, enzymology
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Research Centre: Neglected Tropical Diseases Network
PubMed ID: 12049643
Web of Science ID: 176552600023
URI: http://researchonline.lshtm.ac.uk/id/eprint/16479

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