Trypanosoma cruzi expresses a plant-like ascorbate-dependent hemoperoxidase localized to the endoplasmic reticulum


Wilkinson, SR; Obado, SO; Mauricio, IL; Kelly, JM; (2002) Trypanosoma cruzi expresses a plant-like ascorbate-dependent hemoperoxidase localized to the endoplasmic reticulum. Proceedings of the National Academy of Sciences of the United States of America, 99 (21). pp. 13453-8. ISSN 0027-8424 DOI: https://doi.org/10.1073/pnas.202422899

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Abstract

In most aerobic organisms hemoperoxidases play a major role in H(2)O(2)-detoxification, but trypanosomatids have been reported to lack this activity. Here we describe the properties of an ascorbate-dependent hemoperoxidase (TcAPX) from the American trypanosome Trypanosoma cruzi. The activity of this plant-like enzyme can be linked to the reduction of the parasite-specific thiol trypanothione by ascorbate in a process that involves nonenzymatic interaction. The role of heme in peroxidase activity was demonstrated by spectral and inhibition studies. Ascorbate could saturate TcAPX activity indicating that the enzyme obeys Michaelis-Menten kinetics. Parasites that overexpressed TcAPX activity were found to have increased resistance to exogenous H(2)O(2). To determine subcellular location an epitope-tagged form of TcAPX was expressed in T. cruzi, which was observed to colocalize with endoplasmic reticulum resident chaperone protein BiP. These findings identify an arm of the oxidative defense system of this medically important parasite. The absence of this redox pathway in the human host may be therapeutically exploitable.

Item Type: Article
Keywords: Amino Acid Sequence, Animal, Ascorbic Acid/metabolism, Base Sequence, Comparative Study, DNA, Protozoan/genetics, Endoplasmic Reticulum/enzymology, Genes, Protozoan, Human, Hydrogen Peroxide/metabolism/pharmacology, Molecular Sequence Data, Oxidation-Reduction, Peroxidases/chemistry/genetics/*metabolism, Plants/enzymology, Sequence Homology, Amino Acid, Support, Non-U.S. Gov't, Trypanosoma cruzi/drug effects/*enzymology/genetics, Amino Acid Sequence, Animal, Ascorbic Acid, metabolism, Base Sequence, Comparative Study, DNA, Protozoan, genetics, Endoplasmic Reticulum, enzymology, Genes, Protozoan, Human, Hydrogen Peroxide, metabolism, pharmacology, Molecular Sequence Data, Oxidation-Reduction, Peroxidases, chemistry, genetics, metabolism, Plants, enzymology, Sequence Homology, Amino Acid, Support, Non-U.S. Gov't, Trypanosoma cruzi, drug effects, enzymology, genetics
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
PubMed ID: 12351682
Web of Science ID: 178635700022
URI: http://researchonline.lshtm.ac.uk/id/eprint/16480

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