Article
Plasmodium falciparum antioxidant protein as a model enzyme for a special class of glutaredoxin/glutathione-dependent peroxiredoxins
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Published: | January 29, 2014 |
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The growth of the human malaria parasite Plasmodium falciparum within red blood cells is postulated to depend on the ability to remove reactive oxygen species. In the absence of catalase and classical glutathione peroxidases, peroxiredoxins have been suggested to play a crucial role for the parasite’s antioxidant defense [1]. Peroxiredoxins are a heterogeneous family of thiolperoxidases, which utilize one or two cysteine residues to reduce hydroperoxides. For most peroxiredoxins, the electron donor is thioredoxin. One of the five P. falciparum peroxiredoxins, Plasmodium falciparum Antioxidant Protein (PfAOP), has been partially described in vitro. Although its physiological role remains unknown, PfAOP was shown to preferentially use an electron donor system consisting of glutaredoxin and glutathione (GSH) [1]. We now dissected the unusual mechanism of PfAOP in vitro [2]: Our data clearly reveal that PfAOP acts via a ping-pong mechanism using P. falciparum glutaredoxin (PfGrx) and GSH as true substrates. Only one PfAOP cysteine residue and one PfGrx cysteine residue are sufficient for catalysis. Thus, PfGrx is not just a simple replacement of thioredoxin. Our data also point to a GSH-dependent enzyme activation and a negative subunit cooperativity of PfAOP. In silico analyses furthermore suggest that PfAOP is a member of a special subclass of glutaredoxin/GSH-dependent peroxiredoxins. This subclass might be the result of a peculiar molecular evolution that helped malaria parasites and other pathogens to cope with reactive oxygen species.
References
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- Deponte M, Rahlfs S, Becker K. Peroxiredoxin systems of protozoal parasites. In: Flohé L, Harris JR, editors. Peroxiredoxin Systems. New York: Springer; 2007. 219-29. (Subcellular Biochemistry; 44). DOI: 10.1007/978-1-4020-6051-9_10
- 2.
- Djuika CF, Fiedler S, Schnölzer M, Sanchez C, Lanzer M, Deponte M. Plasmodium falciparum antioxidant protein as a model enzyme for a special class of glutaredoxin/glutathione-dependent peroxiredoxins. Biochim Biophys Acta. 2013 Aug;1830(8):4073-90. DOI: 10.1016/j.bbagen.2013.04.020