In the apicoplast of apicomplexan parasites, plastidic-type ferredoxin and ferredoxin-NADP+ reductase (FNR) form a short electron transport chain that provides reducing power for the synthesis of isoprenoid precursors. These proteins are attractive targets for the development of novel drugs against diseases such as malaria, toxoplasmosis, and coccidiosis. We have obtained ferredoxin and FNR of both Toxoplasma gondii and Plasmodium falciparum in recombinant form, and recently we solved the crystal structure of the P. falciparum reductase. Here we report on the functional properties of the latter enzyme, which differ markedly from those of homologous FNRs. In the physiological reaction, P. falciparum FNR displays a kcat five-fold lower than those usually determined for plastidic-type FNRs. By rapid kinetics, we found that hydride transfer between NADPH and protein-bound FAD is slower in the P. falciparum enzyme. The redox properties of the enzyme were determined, and showed that the FAD semiquinone species is highly destabilized. We propose that these two features, i.e. slow hydride transfer and unstable FAD semiquinone, are responsible for the poor catalytic efficiency of the P. falciparum enzyme. Another unprecedented feature of the malarial parasite FNR is its ability to yield, under oxidizing conditions, an inactive dimeric form stabilized by an intermolecular disulfide bond. Here we show that the monomer–dimer interconversion can be controlled by oxidizing and reducing agents that are possibly present within the apicoplast, such as H2O2, glutathione, and lipoate. This finding suggests that modulation of the quaternary structure of P. falciparum FNR might represent a regulatory mechanism, although this needs to be verified in vivo.
The ferredoxin-NADP+ reductase/ferredoxin electron transfer system of Plasmodium falciparum / E. Balconi, A. Pennati, D. Crobu, V.E. Pandini, R. Cerutti, G. Zanetti, A. Aliverti. - In: THE FEBS JOURNAL. - ISSN 1742-464X. - 276:14(2009 Jul), pp. 3825-3836.
|Titolo:||The ferredoxin-NADP+ reductase/ferredoxin electron transfer system of Plasmodium falciparum|
BALCONI, EMANUELA (Primo)
PENNATI, ANDREA (Secondo)
ZANETTI, GIULIANA (Penultimo)
ALIVERTI, ALESSANDRO (Ultimo)
|Parole Chiave:||Disulfide; Enzyme; Flavoprotein; Hydride transfer; Malaria|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Data di pubblicazione:||lug-2009|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1111/j.1742-4658.2009.07100.x|
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