TAILIEUCHUNG - Báo cáo khoa học: The ferredoxin-NADP+ reductase ⁄ferredoxin electron transfer system of Plasmodium falciparum

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. | ỊFEBS Journal The ferredoxin-NADP reductase ferredoxin electron transfer system of Plasmodium falciparum Emanuela Balconi Andrea Pennati Danila Crobu Vittorio Pandini Raffaele Cerutti Giuliana Zanetti and Alessandro Aliverti Dipartimento di Scienze Biomolecolari e Biotecnologie Universita degli Studi di Milano Italy Keywords disulfide enzyme flavoprotein hydride transfer malaria Correspondence A. Aliverti Dipartimento di Scienze Biomolecolari e Biotecnologie University degli Studi di Milano via Celoria 26 20133 Milano Italy Fax 39 02 50314895 Tel 39 02 50314897 E-mail Website http Present address Department of Chemistry Georgia State University Atlanta GA USA Received 18 March 2009 revised 30 April 2009 accepted 13 May 2009 doi 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 proteinbound 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 . slow hydride transfer and unstable FAD semiquinone are responsible for the poor catalytic efficiency of the P.

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