Document Detail


Mycobacterium tuberculosis FprA, a novel bacterial NADPH-ferredoxin reductase.
MedLine Citation:
PMID:  12071965     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The gene fprA of Mycobacterium tuberculosis, encoding a putative protein with 40% identity to mammalian adrenodoxin reductase, was expressed in Escherichia coli and the protein purified to homogeneity. The 50-kDa protein monomer contained one tightly bound FAD, whose fluorescence was fully quenched. FprA showed a low ferric reductase activity, whereas it was very active as a NAD(P)H diaphorase with dyes. Kinetic parameters were determined and the specificity constant (kcat/Km) for NADPH was two orders of magnitude larger than that of NADH. Enzyme full reduction, under anaerobiosis, could be achieved with a stoichiometric amount of either dithionite or NADH, but not with even large excess of NADPH. In enzyme titration with substoichiometric amounts of NADPH, only charge transfer species (FAD-NADPH and FADH2-NADP+) were formed. At NADPH/FAD ratios higher than one, the neutral FAD semiquinone accumulated, implying that the semiquinone was stabilized by NADPH binding. Stabilization of the one-electron reduced form of the enzyme may be instrumental for the physiological role of this mycobacterial flavoprotein. By several approaches, FprA was shown to be able to interact productively with [2Fe-2S] iron-sulfur proteins, either adrenodoxin or plant ferredoxin. More interestingly, kinetic parameters of the cytochrome c reductase reaction catalyzed by FprA in the presence of a 7Fe ferredoxin purified from M. smegmatis were determined. A Km value of 30 nm and a specificity constant of 110 microM(-1) x s(-1) (10 times greater than that for the 2Fe ferredoxin) were determined for this ferredoxin. The systematic name for FprA is therefore NADPH-ferredoxin oxidoreductase.
Authors:
Federico Fischer; Debora Raimondi; Alessandro Aliverti; Giuliana Zanetti
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of biochemistry / FEBS     Volume:  269     ISSN:  0014-2956     ISO Abbreviation:  Eur. J. Biochem.     Publication Date:  2002 Jun 
Date Detail:
Created Date:  2002-06-19     Completed Date:  2002-08-19     Revised Date:  2007-07-23    
Medline Journal Info:
Nlm Unique ID:  0107600     Medline TA:  Eur J Biochem     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  3005-13     Citation Subset:  IM    
Affiliation:
Dipartimento di Fisiologia e Biochimica Generali, Università degli Studi di Milano, Milano, Italy.
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MeSH Terms
Descriptor/Qualifier:
Anaerobiosis
Bacterial Proteins / chemistry*,  genetics,  metabolism
Catalysis
Electron Transport / physiology
Ferredoxin-NADP Reductase / chemistry*,  genetics,  metabolism*
Ferredoxins / isolation & purification,  metabolism*
Flavoproteins / chemistry,  metabolism*
Mycobacterium tuberculosis / enzymology*
Oxidation-Reduction
Recombinant Proteins / chemistry,  genetics,  metabolism
Chemical
Reg. No./Substance:
0/Bacterial Proteins; 0/Ferredoxins; 0/Flavoproteins; 0/Recombinant Proteins; EC 1.18.1.2/Ferredoxin-NADP Reductase

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