Disease relevance of FDX1

• To probe the function of Thr-49 in a vertebrate ferredoxin, replacement mutants T49A, T49S, T49L, and T49Y, and a deletion mutant, T49Delta, were generated and expressed in Escherichia coli [1].
• The structure of Fdx is similar to the structures of bovine adrenodoxin (Adx) and Pseudomonas putida putidaredoxin (Pdx) whose respective root-mean-square deviations of the corresponding Calpha atoms are 1.8 and 2.2 A [2].
• The UV-visible and EPR spectra of the [2Fe-2S] cluster indicate that HndA belongs to the [2Fe-2S] family typified by the Clostridium pasteurianum [2Fe-2S] ferredoxin [3].
• 2. Ferredoxin I of Azotobacter vinelandii [4].
• 3. Ferredoxin II of Desulfovibrio gigas [4].

Psychiatry related information on FDX1

• Spinach ferredoxin and adrenodoxin were found to differ substantially with regard to their metal-substitution reactivity under oxidizing and reducing conditions, reaction time, and formation of apoprotein, which was more pronounced for spinach ferredoxin [5].

High impact information on FDX1

• Phosphorylation of ferredoxin and regulation of renal mitochondrial 25-hydroxyvitamin D-1 alpha-hydroxylase activity in vitro [6].
• These findings suggest that phosphorylation/dephosphorylation of Fx may play a role in modulating renal 1,25-dihydroxyvitamin D production [6].
• Peptide mapping of phosphorylated Fx was consistent with phosphorylation of serine 88 and threonine 85 or 97 [6].
• Amino acid analysis demonstrated that 1 mol of serine and 1 mol of threonine were phosphorylated per mol of Fx [6].
• Fx was selectively dephosphorylated by rabbit skeletal muscle protein phosphatase C2 but not C1 [6].

Chemical compound and disease context of FDX1

• Escherichia coli ferredoxin (Fdx) is an adrenodoxin-type [2Fe-2S] ferredoxin [2].
• The reaction of potassium ferricyanide with protein-bound iron atoms to form royal blue complexes occurs almost instantaneously and is sensitive enough to detect 1 microgram of analytical-grade ferritin and 2 micrograms of purified ferredoxin from cyanobacteria [7].

Biological context of FDX1

• Molecular cloning and nucleotide sequences of bovine hepato-ferredoxin cDNA; identical primary structures of hepato- and adreno-ferredoxins [8].
• 5. Identical amino acid sequence of the two ferredoxins was confirmed by determining the partial amino acid sequence of the purified hepato-ferredoxin [8].
• Assignment of ferredoxin 1 (FDX1) to bovine chromosome 15 with somatic cell hybrids [9].
• Fdx probably functions as a component of the complex machinery responsible for the biogenesis of Fe-S clusters [2].
• The cDNAs of AdR and Adx on the first plasmid were separated by a ribosome binding sequence, with the reductase preceding the ferredoxin [10].

Anatomical context of FDX1

• NADPH-ferredoxin reductase and ferredoxin activities have been identified in bovine thyroid particulate fractions (mainly mitochondria) after ultrasonication and DEAE-cellulose chromatography [11].
• Ferredoxin and ferredoxin reductase activities in bovine thyroid. Possible relationship to iodotyrosine deiodinase [11].
• 1. The ferredoxin from bovine liver mitochondria, so-called hepatoredoxin, was purified and characterized as to its molecular weight, optical absorption spectrum and amino acid composition [8].
• Mature bovine adrenocortical ferredoxin (adreno-ferredoxin) was extracted from fresh adrenal glands at pH 9 [12].
• However, this mRNA in the adrenal cell line, Y-1 cell, was not induced by adenosine 3',5'-cyclic monophosphate (cAMP) in contrast with ferredoxin mRNA [13].

Associations of FDX1 with chemical compounds

• NADPH ferredoxin reductase and ferredoxin also catalyzed NADPH-dependent deiodination of L-diiodotyrosine; bovine adrenodoxin and adrenodoxin reductase could partially replace the thyroidal components in NADPH-dependent deiodination of L-diiodotyrosine [11].
• In the presence of adrenoxodin reductase, NADPH, and carbon monoxide, the purified renal ferredoxin was found to be active in the reduction of cytochrome P-450 solubilized from chick kidney mitochondria [14].
• Crystallographic analysis of a fully functional, truncated bovine adrenodoxin, Adx(4-108), has revealed the structure of a vertebrate-type [2Fe-2S] ferredoxin at high resolution [15].
• It has been proposed for bovine ferredoxin that His56 hydrogen bonds with a labile sulfur and that the reduction of the iron-sulfur center is accompanied by the uptake of a proton by this histidine [Lambeth, J. D., Seybert, D. W., Lancaster, J. R., Jr., Salerno, J. C., & Kamin, H. (1982) Mol. Cell. Biochem. 45, 13-31] [16].
• Adrenodoxin (Adx) is a [2Fe-2S] ferredoxin involved in electron transfer reactions in the steroid hormone biosynthesis of mammals [17].

Other interactions of FDX1

• Ferredoxin reductase and ferredoxin were purified from the bovine corpus luteum and their properties compared to the corresponding adrenal proteins [18].
• Parathyroid hormone stimulates the renal conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D in young animals, which is accompanied by dephosphorylation of ferredoxin (Fx), a component of the mitochondrial 1-OHase enzyme complex (Siegel, N., Wongsurawat, N., and Armbrecht, H. J. (1986) J. Biol. Chem. 261, 16998-17003) [6].
• A biologically active spinach ferredoxin was reconstituted from the apoprotein by incubation with catalytic amounts of the sulfurtransferase rhodanese in the presence of thiosulfate, reduced lipoate and ferric ammonium citrate [19].
• It was recently shown that the TYKY subunit is not an ordinary 2[4Fe-4S] ferredoxin, but has a unique amino acid sequence, which is only found in NAD(P)H:quinone oxidoreductases and certain membrane-bound [NiFe]-hydrogenases expected to be involved in redox-linked proton translocation [FEBS Lett. 485 (2000) 1] [20].

Analytical, diagnostic and therapeutic context of FDX1

• The purified adreno-ferredoxin was homogeneous on the basis of two HPLC analyses, hydrophobic and ion exchange, and had the highest purity so far reported [12].
• Evidence was obtained from spectrophotometric titrations for formation of 1:1 complexes between luteal ferredoxin reductase and ferredoxin and between ferredoxin and cytochrome P-450scc [18].
• Phosphorylation did not alter Fx mobility on sodium dodecyl sulfate gels but did decrease the pI as measured by isoelectric focusing [6].
• Absorption, circular dichroism, fluorescence, and electron paramagnetic resonance spectra of mutant T54S show that this substitution has no influence on the formation and stability of the ferredoxin [21].
• A mol. wt. of 53 000 was determined by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and by Sephadex G-100 gel filtration of the 125I-labelled ferredoxin [22].

References