Structural and functional diversity of ferredoxin-NADP+ reductases

Abstract

Although all ferredoxin-NADP+ reductases (FNRs) catalyze the same reaction. i. e. the transfer of reducing equivalents between NADP(H) and ferredoxin, they belong to two unrelated families of proteins: the plant type and the glutathione reductase type of FNRs. Aim of this review is to provide a general classification scheme for these enzymes, to be used as a framework for the comparison of their properties.Furthermore, we report on some recent findings, which significantly increased the understanding of the structure-function relationships of FNRs, i.e. the ability of adrenodoxin reductase and its homologs to catalyze the oxidation of NADP+ to its 4-oxo derivative, and the properties of plant-type FNRs from non- Subject: revision of ms ABBI-07-950Dear Editor, we would like to thank the Reviewers for their criticisms and suggestions that hopefully allowed us to improve our article. We carefully revised the manuscript according to the Reviewer's suggestions. The overall length of the paper has been significantly reduced by shortening longer chapters and by deleting three figures.The major changes in the revised version of the manuscript are as follows: Fig. 1, GR-type FNRs represent a broader group that include both the AdR-like and the ONFR-like enzymes. Thus, we prefer to maintain the distinction between the two terms (GR-type and AdR-like).2) While most of the chapters have similar lengths, the last two chapters are significantly longer than the previous six ones, creating an unpleasant imbalance in the presentation. The authors should try to either condense or split in multiple chapters the two long ones, in order to have a more armonious and balanced presentation of the topics. Large chapters ("Specific features of Plasmodium falciparum FNR" and "Ferredoxin binding and electron-transfer") were significantly shortened (by 35% and 22%, respectively). Previous very long paragraphs were broken into smaller ones.3) The work would significantly gain in strength upon adding a small summary paragraph at the end of the review article. Alternatively, the authors may consider a paragraph in which they present open questions that can now be raised and answered based upon current knowledge. A Conclusion chapter has been added. However, in order to limit the ms length, this chapter is not a summary or a list of open questions, but includes just some concluding remarks. 5) A list of abbreviations should be included. For example, what is NMN?A list of abbreviations has been added. 6) On page 4 line 15, both n and S should be defined.The definition of the parameters n and S has been given, and a reference added. 7) The authors should specify clearly which enzymes have been wrongly identified as adrenodoxin reductase-like enzymes (page 6).What we found is that some AdR-like proteins have been wrongly identified as other enzymes, and not the opposite. We think that, for the sake of brevity, it is not possible to give a comprehensive list of incorrectly identified entries within this review article. We have provide...

Studies of interaction of homo-dimeric ferredoxin-NAD(P)+ oxidoreductases of Bacillus subtilis and Rhodopseudomonas palustris, that are closely related to thioredoxin reductases in amino acid sequence, with ferredoxins and pyridine nucleotide coenzymes

“…Because FNRs have multiple phylogenetic origins, comparative studies of different FNR group enzymes with respect to the mechanisms regulating substrate binding and catalytic properties are necessary for a deeper understanding of the structure-function relationships of FNR. With monomeric FNRs of the plastid-type and the mitochondria-type, substrate binding and reaction mechanisms have been extensively studied [for reviews, see 6,7,10,21]. However, few such studies have been reported on the proteobacteria-type [14,15] and no such studies have been reported on the Firmicutes and green sulfur bacteria-type FNRs.…”

“…This architecture is typical of the NAD(P) + /NAD(P)H-linked flavoenzyme family including disulfide reductases such as glutathione reductase and thioredoxin reductase [5][6][7]20]. Because FNRs have multiple phylogenetic origins, comparative studies of different FNR group enzymes with respect to the mechanisms regulating substrate binding and catalytic properties are necessary for a deeper understanding of the structure-function relationships of FNR.…”

Role of the C-terminal extension stacked on the re-face of the isoalloxazine ring moiety of the flavin adenine dinucleotide prosthetic group in ferredoxin-NADP+ oxidoreductase from Bacillus subtilis

“…+ oxidoreductase ([EC 1.18.1.2], [EC 1.18.1.3], FNR) is a member of the dehydrogenase family of the flavoprotein superfamily (Aliverti et al, 2008;Dym and Eisenberg, 2001;Correll et al, 1993). FNR catalyzes the redox reaction between the two electron carrier nucleotides, NAD(P)H, and the one electron carrier iron-sulfur proteins, ferredoxin (Fd), adrenodoxin (Ad) and putidaredoxin (Pd), and also the low molecular weight flavoprotein, flavodoxin.…”

Replacement of Tyr50 stacked on the si-face of the isoalloxazine ring of the flavin adenine dinucleotide prosthetic group modulates Bacillus subtilis ferredoxin-NADP+ oxidoreductase activity toward NADPH

“…Fd is ubiquitous in almost all organisms, functioning as an electron mediator in cytochrome P450 dependent hydroxylation, nitrogen assimilation, and NADP + reduction from reduced Fd during photosynthesis (Aliverti et al 2008;Ceccarelli et al 2004;Munro et al 2007; Knaff and Hirasawa 1991;Ewen et al 2011). FNR, a member of the flavoprotein superfamily, contains a flavin adenine dinucleotide (FAD) or rarely, FMN as the prosthetic group.…”

“…FNRs are structurally and phylogenetically classified into two unrelated families including five subgroups (Aliverti et al 2008;Dym and Eisenberg 2001;Correll et al 1993;Karplus and Faber 2004;Seo et al 2004;Muraki et al 2010). Phylogenetic analyses of the deduced amino acid sequences (Seo et al 2004) and crystal structures of FNRs from the green sulfur bacterium Chlorobaculum tepidum (Muraki et al 2010), the low GC gram positive bacterium Bacillus subtilis (BsFNR, Komori et al 2010) and thermophile Thermus thermophiles (PDB code; 2ZBW) have revealed that these FNRs are homologous to the NADPH-dependent bacterial thioredoxin reductase (TrxR) from Escherichia coli (EcTrxR) (Waksman et al 1994), referred as a TrxR-type FNR.…”