The ferredoxin-NADP+ reductase/ferredoxin electron transfer system of Plasmodium falciparum.

Publisher: Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies Country of Publication: England NLM ID: 101229646 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1742-4658 (Electronic) Linking ISSN: 1742464X NLM ISO Abbreviation: FEBS J Subsets: MEDLINE

Original Publication: Oxford, UK : Published by Blackwell Pub. on behalf of the Federation of European Biochemical Societies, c2005-

Protein Multimerization*; Ferredoxin-NADP Reductase/*metabolism ; Ferredoxins/*metabolism ; Plasmodium falciparum/*metabolism ; Protozoan Proteins/*metabolism; Anaerobiosis ; Animals ; Biocatalysis ; Cloning, Molecular ; Crystallography, X-Ray ; Electron Transport ; Ferredoxin-NADP Reductase/chemistry ; Ferredoxin-NADP Reductase/genetics ; Flavin-Adenine Dinucleotide/metabolism ; Horses ; Kinetics ; Models, Molecular ; Osmolar Concentration ; Oxidation-Reduction ; Protein Binding ; Protein Structure, Quaternary ; Protozoan Proteins/chemistry ; Protozoan Proteins/genetics

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 k(cat) 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 monomerdimer interconversion can be controlled by oxidizing and reducing agents that are possibly present within the apicoplast, such as H(2)O(2), 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.

0 (Ferredoxins)
0 (Protozoan Proteins)
146-14-5 (Flavin-Adenine Dinucleotide)
EC 1.18.1.2 (Ferredoxin-NADP Reductase)

Date Created: 20090616 Date Completed: 20091013 Latest Revision: 20220318

20250114

10.1111/j.1742-4658.2009.07100.x

19523113