Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hemoglobin of yeast is a two-domain protein with both heme and flavin prosthetic groups. The nucleotide sequences of the cDNA and genomic DNA encoding the protein from Saccharomyces cerevisiae show that introns are absent and that both domains are homologous with a flavoheme protein from Escherichia coli. The heme domains are also homologous with those of O2-binding heme proteins from several other distantly related bacteria, plants, and animals; all appear to be members of the same globin superfamily. Although the homologous hemoglobin of the bacterium Vitreoscilla sp. is a single-domain protein, several bacteria have related O2-binding heme proteins whose second domains have different structures and enzymatic activities: dihydropteridine reductase (E. coli), cytochrome c reductase (Alcaligenes eutrophus), and kinase in the O2 sensor of Rhizobium meliloti. This indicates that one evolutionary pathway of hemoglobin is that of a multipurpose domain attached to a variety of unrelated proteins to form molecules with different functions. The flavin domain of yeast hemoglobin is homologous with members of a flavoprotein family that includes ferredoxin reductase, nitric oxide synthase, and cytochrome P-450 reductase. The correspondence of yeast and E. coli flavohemoglobins indicates that the two-domain protein has been conserved intact for as long as 1.8 billion years, the estimated time of divergence of prokaryotes and eukaryotes provided that cross-species gene transfer has not occurred.
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PMID:Yeast flavohemoglobin is an ancient protein related to globins and a reductase family. 159 8

Soluble extracts of Escherichia coli contain four NADPH:paraquat diaphorases that were separable by anion-exchange HPLC over Mono Q. One of these was induced when the cells were exposed to paraquat. This was the case in a soxRS-competent strain but not in a soxRS-null strain, while a soxRS-constitutive strain overexpressed this diaphorase without the stimulus of exposure to paraquat. This NADPH:paraquat diaphorase could use cytochrome c or nitroblue tetrazolium as an electron acceptor, whereas O2 was a relatively poor acceptor. This diaphorase was identified as the NADPH:ferredoxin reductase. A role for reduced ferredoxin and flavodoxin in the adaptive soxRS response to oxidative stress and in the regulation of the redox status of soxR is discussed.
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PMID:NADPH: ferredoxin oxidoreductase acts as a paraquat diaphorase and is a member of the soxRS regulon. 810 11

Cytochromes P450 utilize redox partners to deliver electrons from NADPH/NADH to the P450 heme center. Microsomal P450s utilize an FAD/FMN reductase. The bacterial fatty acid hydroxylase, P450BM-3, is similar except the P450 heme and FAD/FMN proteins are linked together in a single polypeptide chain arranged as heme-FMN-FAD. Sequence comparisons indicate that the P450BM-3 FMN and FAD domains are similar to flavodoxin and ferredoxin reductase, respectively. Previous work has shown that the heme and FMN/FAD domains can be separately expressed and purified. In this study we have expressed, purified, and characterized the following additional domains: heme-FMN, FMN, and FAD. Each domain retains their prosthetic groups although the FMN domain is more labile. The FAD domain retains a high level of ferricyanide reductase activity but no cytochrome c reductase activity. In addition, we have deleted a 110-residue stretch in the FAD domain that is not present in ferredoxin reductase. This protein retains both FAD and heme but not FMN. We also have investigated the dimerization pattern of the individual domains that lead to the following conclusions. Holo-P450BM-3 appears to dimerize via interactions that do not involve disulfide bond formation, whereas the reductase and FAD domains form intermolecular disulfides. This indicates that the Cys residues not available for dimerization in holo-P450BM-3 are unmasked in the individual domains.
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PMID:The domain architecture of cytochrome P450BM-3. 906 59