Ferredoxin-NADP+ reductase (FNR, EC 22.214.171.124) 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 ; A. Aliverti, G. Zanetti. - Milano : Università degli studi di Milano. DIPARTIMENTO DI SCIENZE BIOMOLECOLARI E BIOTECNOLOGIE, 2007. ((20. ciclo, Anno Accademico 2006/2007.
|Titolo:||Characterization of ferredoxin-NADP+ reductases from pathogenic microorganisms|
|Supervisori e coordinatori interni:||ZANETTI, GIULIANA|
|Data di pubblicazione:||2007|
|Parole Chiave:||Mycobacterium tuberculosis ; Plasmodium falciparum ; Toxoplasma gondii ; malaria ; drug target ; drug design ; enzyme ; flavoprotein ; enzyme inhibitor|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Citazione:||Characterization of ferredoxin-NADP+ reductases from pathogenic microorganisms ; A. Aliverti, G. Zanetti. - Milano : Università degli studi di Milano. DIPARTIMENTO DI SCIENZE BIOMOLECOLARI E BIOTECNOLOGIE, 2007. ((20. ciclo, Anno Accademico 2006/2007.|
|Appare nelle tipologie:||13 - Tesi di dottorato discussa entro ottobre 2010|