Ferredoxin-NADP+ reductase (FNR, EC 1.18.1.2) is a functional class of proteins that catalyzes the transfer of electron equivalents from small iron-sulphur proteins (ferredoxin, Fd) to pyridine dinucleotide, or vice versa. Two different, phylogenetically unrelated, subclasses of FNR exist: the plant-like and the mitochondrial FNRs. FprA is a mycobacterial reductase belonging to the latter class. We discovered that FprA is able to catalyse an unusual reaction, leading to the production of a modified NADP, named NADPO. I characterized its production and I showed that this reaction is a hallmark of the mitochondrial-type of FNR. Moreover, in collaboration with the group run by Prof. Bolognesi, we crystallized and solved the structure of a 7Fe ferredoxin, identified as the most probable substrate of FprA. Plan-type FNR has also been found in some human parasites, including Plasmodium falciparum (the causative agent of the tropical malaria). As FNR does not exist in animals but it is important for the parasites, it has been reported to be good drug target for novel therapies against Apicomplexa. In relation to this finding, using different approaches, I looked for inhibitors of this enzyme by screening a phage-display peptide library and by in silico screening of a compound library using the FNR 3D structure as target. Moreover, I characterized some compounds, reported to be good inhibitors of other FNRs or related enzymes.

Characterization of ferredoxin-NADP+ reductases from pathogenic microorganisms / M. De Rosa ; A. Aliverti, G. Zanetti. - : . DIPARTIMENTO DI SCIENZE BIOMOLECOLARI E BIOTECNOLOGIE, 2007. ((20. ciclo, Anno Accademico 2006/2007.

Characterization of ferredoxin-NADP+ reductases from pathogenic microorganisms

M. DE ROSA
2007

Abstract

Ferredoxin-NADP+ reductase (FNR, EC 1.18.1.2) is a functional class of proteins that catalyzes the transfer of electron equivalents from small iron-sulphur proteins (ferredoxin, Fd) to pyridine dinucleotide, or vice versa. Two different, phylogenetically unrelated, subclasses of FNR exist: the plant-like and the mitochondrial FNRs. FprA is a mycobacterial reductase belonging to the latter class. We discovered that FprA is able to catalyse an unusual reaction, leading to the production of a modified NADP, named NADPO. I characterized its production and I showed that this reaction is a hallmark of the mitochondrial-type of FNR. Moreover, in collaboration with the group run by Prof. Bolognesi, we crystallized and solved the structure of a 7Fe ferredoxin, identified as the most probable substrate of FprA. Plan-type FNR has also been found in some human parasites, including Plasmodium falciparum (the causative agent of the tropical malaria). As FNR does not exist in animals but it is important for the parasites, it has been reported to be good drug target for novel therapies against Apicomplexa. In relation to this finding, using different approaches, I looked for inhibitors of this enzyme by screening a phage-display peptide library and by in silico screening of a compound library using the FNR 3D structure as target. Moreover, I characterized some compounds, reported to be good inhibitors of other FNRs or related enzymes.
ALIVERTI, ALESSANDRO
ZANETTI, GIULIANA
Mycobacterium tuberculosis ; Plasmodium falciparum ; Toxoplasma gondii ; malaria ; drug target ; drug design ; enzyme ; flavoprotein ; enzyme inhibitor
Settore BIO/10 - Biochimica
Characterization of ferredoxin-NADP+ reductases from pathogenic microorganisms / M. De Rosa ; A. Aliverti, G. Zanetti. - : . DIPARTIMENTO DI SCIENZE BIOMOLECOLARI E BIOTECNOLOGIE, 2007. ((20. ciclo, Anno Accademico 2006/2007.
Doctoral Thesis
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/59919
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