Information on EC 1.3.5.4 - fumarate reductase (quinol)

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
1.3.5.4
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RECOMMENDED NAME
GeneOntology No.
fumarate reductase (quinol)
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
succinate + a quinone = fumarate + a quinol
show the reaction diagram
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
anaerobic energy metabolism (invertebrates, mitochondrial)
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Biosynthesis of antibiotics
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Biosynthesis of secondary metabolites
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Butanoate metabolism
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Carbon fixation pathways in prokaryotes
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Citrate cycle (TCA cycle)
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glycerol-3-phosphate to fumarate electron transfer
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hydrogen to fumarate electron transfer
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incomplete reductive TCA cycle
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Metabolic pathways
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Microbial metabolism in diverse environments
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mixed acid fermentation
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NADH to fumarate electron transfer
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partial TCA cycle (obligate autotrophs)
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pyruvate fermentation to propanoate I
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Pyruvate metabolism
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reductive TCA cycle I
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reductive TCA cycle II
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TCA cycle VIII (helicobacter)
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SYSTEMATIC NAME
IUBMB Comments
succinate:quinone oxidoreductase
The enzyme, which is found in anaerobic and facultative organisms such as bacteria, parasitic helminthes, and lower marine organisms, utilizes low potential quinols, such as menaquinol and rhodoquinol, to reduce fumarate as the final step of an anaerobic respiratory chain. The enzyme is known as complex II of the electron transfer chain, similarly to EC 1.3.5.1, succinate dehydrogenase (quinone), to which it is closely related.
CAS REGISTRY NUMBER
COMMENTARY hide
9076-99-7
cf EC 1.3.1.6
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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UniProt
Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2,3-dimethyl-1,4-naphthoquinol + fumarate
?
show the reaction diagram
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-
-
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?
fumarate + 2,3-dimethyl-1,4-naphthohydroquinone
succinate + 2,3-dimethyl-1,4-naphthoquinone
show the reaction diagram
fumarate + 8-methylmenaquinol-6
succinate + 8-methylmenaquinone-6
show the reaction diagram
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-
-
-
?
fumarate + a menaquinol
succinate + a menaquinone
show the reaction diagram
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the enzyme is involved in anaerobic metabolism
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?
fumarate + anthrahydroquinonesulfonate
succinate + anthraquinonesulfonate
show the reaction diagram
fumarate + menaquinol
succinate + ?
show the reaction diagram
fumarate + menaquinol
succinate + menaquinone
show the reaction diagram
fumarate + menaquinol-6
succinate + menaquinone-6
show the reaction diagram
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-
-
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r
succinate + a menaquinone
fumarate + a menaquinol
show the reaction diagram
succinate + menaquinone
fumarate + menaquinol
show the reaction diagram
succinate + methylene blue
?
show the reaction diagram
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-
-
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?
succinate + phenazine methosulfate
fumarate + reduced phenazine methosulfate
show the reaction diagram
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-
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r
succinate + phenazine methosulfate + 2,6-dichlorophenolindophenol
fumarate + ?
show the reaction diagram
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quinone reduction by Rhodothermus marinus succinate:menaquinone oxidoreductase is not stimulated by the membrane potential
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-
?
succinate + rhodoquinone
fumarate + rhodoquinol
show the reaction diagram
additional information
?
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
fumarate + 2,3-dimethyl-1,4-naphthohydroquinone
succinate + 2,3-dimethyl-1,4-naphthoquinone
show the reaction diagram
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-
-
?
fumarate + a menaquinol
succinate + a menaquinone
show the reaction diagram
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the enzyme is involved in anaerobic metabolism
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?
fumarate + menaquinol
succinate + menaquinone
show the reaction diagram
succinate + a menaquinone
fumarate + a menaquinol
show the reaction diagram
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the enzyme is involved in anaerobic respiration with fumarate as the terminal electron acceptor, and is part of an electron transport chain catalysing the oxidation of various donor substrates by fumarate
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?
succinate + rhodoquinone
fumarate + rhodoquinol
show the reaction diagram
P92507
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?
additional information
?
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the fumarate reductase complex has two different reactive sites, which are essential for its function in the phosphorylative electron transport of the bacterium
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cytochrome b
heme b
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the enzyme contains one hydrophobic subunit (menaquinol-oxidising subunit C) with two haem b groups. The binding of the two heme molecules is described. The close proximity between the two hemes offers a straightforward possibility for transmembrane electron transfer
iron-sulfur centre
menaquinol-6
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additional information
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Fe2+
of the three iron-sulfur centres bound to subunit Ip, [2Fe-2S] is coordinated by four cysteine residues,B89, B94, B97 and B109, and located in the N-terminal domain, whereas [4Fe-4S] and [3Fe-4S] that are coordinated by four, B182, B185, B188, and B249, and three, B192, B239 and B245, cysteine residues, respectively, are bound to the C-terminal domain. These iron-sulfur centres are also surrounded with highly conserved hydrophobic amino acid residues
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-(n-heptyl)-4-hydroxy-quinoline N-oxide
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2-heptyl-4-hydroxyquinoline N-oxide
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inhibitor blocks the binding of menaquinol at the proximal quinone binding-site, crystallization studies
2-n-heptyl-4-hydroxyquinoline-N-oxide
2-[1-(p-chlorophenyl)ethyl] 4,6-dinitrophenol
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inhibitor blocks the binding of menaquinol at the proximal quinone binding-site, crystallization studies
4-Chloromercuriphenyl sulfonate
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inhibits the succinate oxidation by cell-derived particles
4-Chloromercuriphenylsulfonate
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inhibits the oxidation of reduced menaquinone by fumarate. Fumarate reductase, measured with reduced benzylviologen as the donor, is not affected
antimycin A
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site of inhibition is located at the oxidation side of cytochrome b
malonate
oxaloacetate
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Pentachlorophenol
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additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.12
2,3-dimethyl-1,4-naphthohydroquinone
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0.0054 - 0.03
fumarate
0.0018 - 0.004
menaquinone
0.33
phenazine methosulfate
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pH 7.6, 30C
0.0015 - 0.64
succinate
additional information
succinate
fumarate reduction. 0.0013 mM, with ubiquinone, reaction of succinate-ubiquinone oxidase EC 1.3.5.1
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.3 - 250
fumarate
77
phenazine methosulfate
Bacillus cereus
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pH 7.6, 30C
0.3 - 80
succinate
additional information
succinate
Escherichia coli
P00363
fumarate reduction. 28 s-1, with ubiquinone, reaction of succinate-ubiquinone oxidase EC 1.3.5.1
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
97 - 232
fumarate
11 - 54
succinate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00006 - 0.0002
2-n-heptyl-4-hydroxyquinoline-N-oxide
0.005 - 0.088
malonate
0.00006 - 0.0003
oxaloacetate
0.023 - 0.037
Pentachlorophenol
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0076
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electron acceptor 2,6-dichlorophenolindophenol, pH 7.6, 30C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH profile analysis, both EC 1.3.5.1 and 1.3.5.4 show a similar profile, suggesting that similar amino acid residues may be involved in quinol deprotonation and oxidation in Escherichia coli enzymes
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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the hydrophilic subunits of the MFR complex are exported into the periplasm via the twin-arginine translocation (tat)-pathway
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Manually annotated by BRENDA team
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soluble fraction contains FMN, acid-extractable FAD, iron-sulfur protein and c cytochromes of the formate-fumarate reductase electron transport system
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Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Shewanella oneidensis (strain MR-1)
Shewanella oneidensis (strain MR-1)
Shewanella oneidensis (strain MR-1)
Wolinella succinogenes (strain ATCC 29543 / DSM 1740 / LMG 7466 / NCTC 11488 / FDC 602W)
Wolinella succinogenes (strain ATCC 29543 / DSM 1740 / LMG 7466 / NCTC 11488 / FDC 602W)
Wolinella succinogenes (strain ATCC 29543 / DSM 1740 / LMG 7466 / NCTC 11488 / FDC 602W)
Wolinella succinogenes (strain ATCC 29543 / DSM 1740 / LMG 7466 / NCTC 11488 / FDC 602W)
Wolinella succinogenes (strain ATCC 29543 / DSM 1740 / LMG 7466 / NCTC 11488 / FDC 602W)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
110000 - 114000
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excluding cytochrome b, calculation from FAD-content and subunit composition
160000 - 167000
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including cytochrome b, calculation from FAD-content and subunit composition
200000
260000
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Blue-native PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oligomer
tetramer
trimer
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purified native enzyme by dialysis method using a reservoir solution containing 15% w/v PEG 3350, 100 mM Tris-HCl, pH 8.4, 200 mM NaCl, 1 mM sodium malonate or fumarate, 0.06% w/v n-dodecyl ethylene glycol monoether C12E8, and 0.04% w/v n-dodecyl-bet-D-maltoside, 2-3 days, X-ray diffraction structure determination and analysis at 2.81-2.91 A resolution, molecular replacement
X-ray diffraction data up to 3.2 resolution
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crystal structure of QFR to 3.3 A resolution. Enzyme contains two quinone species, presumably menaquinol, bound to the transmembrane-spanning region. The binding sites for the two quinone molecules are termed QP and QD, indicating their positions proximal, QP, or distal, QD, to the site of fumarate reduction in the hydrophilic flavoprotein and iron-sulfur protein subunits. Co-crystallization studies of the Escherichia coli QFR with the quinol-binding site inhibitors 2-heptyl-4-hydroxyquinoline-N-oxide and 2-[1-(p-chlorophenyl)ethyl] 4,6-dinitrophenol establish that both inhibitors block the binding of MQH2 at the QP site. In the structures with the inhibitor bound at QP, no density is observed at QD. The conserved acidic residue, Glu29 in subunit FrdC, in the Escherichia coli enzyme may act as a proton shuttle from the quinol during enzyme turnover
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hanging drop vapor diffusion method, x-ray structure of mutant E49Q
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PDB code: 1FUM, structure of the QFR monomer, with the covalently bound FAD cofactor, showing the iron-sulfur clusters [4Fe-4S], [3Fe-3S], and [2Fe-2S] and the two menaquinone molecules
the structure of the enzyme is determined at 2.2 A resolution by X-ray crystallography
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
and reconstitution into proteoliposomes
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native enzyme from muscle mitochondria by anion exchange chromatography
using cell homogenate, Triton X-100 treatment and chromatography on hydroxyapatite and DEAE-Sepharose column
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using solubilization with Triton X-100, chromatography on hydroxyapatite column and DEAE-Sephadex column, the enzyme elutes from the ion-exchange column in two forms, one containing and the other lacking cytochrome b
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloning of a mutant fumarate reductase operon
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expression in Escherichia coli
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gene cluster frdABCD encoding 4 subunits, DNA and amino acid sequence analysis, overepression
two structural genes coding for subunits of the enzyme cloned in Escherichia coli, polarity and organization of the genes
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
fumarate reductase expression is repressed under conditions of growth during which electron transport to oxygen or to nitrate is possible
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fumarate reductase is expressed under anaerobic growth conditions
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sdhABE operon is upregulated in an oxygen-limited environment as compared with microaerophilic laboratory conditions
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the QFR complex provides electron transport during anaerobic cell growth conditions. The transcription of the frdABCD operon responds to environmental as well as internal cell signals to modulate gene expression. The transcription is coupled to that of the succinate-ubiquinone oxidase, EC 1.3.5.1, overview
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C247
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mutation in flavoprotein subunit FrdA. Increase in fumarate reduction rate, slight increase in succinate oxidation. Residue C247 of FrdA is responsible for the N-ethylmaleimide sensitivity shown by fumarate reductase but is not required for catalytic activity or the tight-binding of oxalacetate
E29F
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mutation in subunit FrdC, dramatic decrease in enzymatic reactions with menaqunione. Elimination of the negative charge in E29 mutant enzymes results in significantly increased stabilization of both ubiquinone and menaquinone semiquinones
E29L
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mutation in subunit FrdC, dramatic decrease in enzymatic reactions with menaqunione. Elimination of the negative charge in E29 mutant enzymes results in significantly increased stabilization of both ubiquinone and menaquinone semiquinones
E49A
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decrease in catalytic efficiency of both fumarate reduction and succinate oxidation
E49Q
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decrease in catalytic efficiency of both fumarate reduction and succinate oxidation
H232S
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mutation in flavoprotein subunit FrdA. Decrease in fumarate reduction, strong decrease in succinate oxidation. Residue H232 is the general acid-base catalyst
H82R
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menaquinone, ubiquinone and b-type cytochrome levels are present in normal amounts, the mutation alters the electron transfer properties of the iron-sulfur and flavin redox centers of the catalytic domain, functional electron flow from 2,3-dimethyl-1,4-naphthoquinone or from the electron transport chain is impaired, the mutant can be reduced normally by single-electron donors such as benzyl viologen
K228L
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mutation in subunit FrdB. Residue K228 provides a strong hydrogen bond to menaquinone and is essential for reactions with both ubiquinone and menaquinone
K228R
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mutation in subunit FrdB. Residue K228 provides a strong hydrogen bond to menaquinone and is essential for reactions with both ubiquinone and menaquinone
R248H
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mutation in flavoprotein subunit FrdA. Strong decrease both in fumarate reduction and in succinate oxidation
R248L
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mutation in flavoprotein subunit FrdA. Strong decrease both in fumarate reduction and in succinate oxidation
A86H
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in wild-type enzyme FAD is non-covalenly-bound. In the enzyme containing a mutant A86H flavoprotein subunit the FAD is covalently bound
E180Q
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site-diirected mutagenesis, the mutant catalyzes the electron transfer from succinate to methylene blue, but not from 2,3-dimethyl-1,4-naphthoquinol to fumarate
E66Q
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site-diirected mutagenesis, the mutant catalyzes the electron transfer from succinate to methylene blue, but not from 2,3-dimethyl-1,4-naphthoquinol to fumarate
H44E
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site-diirected mutagenesis, although the H44E variant enzyme retains both heme groups, it is unable to catalyze quinol oxidation, the mutant catalyzes the electron transfer from succinate to methylene blue, with reduced activity compared to the wild-type enzyme but not from 2,3-dimethyl-1,4-naphthoquinol to fumarate
additional information
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
menaquinone is an obligatory redox mediator of formate-fumarate reductase electron transport phosphorylation system. The activity is fully inhibited on the extraction of the menaquinone from the membrane fraction, and is reactivated on reincorporation of menaquinone into the membrane
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the cleavage of the complex causes the complete loss of activity of fumarate reduction by dimethylnaphthohydroquinone, the activity can be restored by coprecipitation of the three subunits of MW: 79000 Da, 31000 Da and 25000 Da
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