Information on EC 1.15.1.1 - superoxide dismutase and Organism(s) Homo sapiens

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EC NUMBER
COMMENTARY hide
1.15.1.1
-
RECOMMENDED NAME
GeneOntology No.
superoxide dismutase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
2 superoxide + 2 H+ = O2 + H2O2
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
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redox reaction
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-
-
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reduction
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-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
ethylene biosynthesis III (microbes)
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reactive oxygen species degradation
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superoxide radicals degradation
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non-pathway related
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SYSTEMATIC NAME
IUBMB Comments
superoxide:superoxide oxidoreductase
A metalloprotein; also known as erythrocuprein, hemocuprein or cytocuprein. Enzymes from most eukaryotes contain both copper and zinc; those from mitochondria and most prokaryotes contain manganese or iron.
CAS REGISTRY NUMBER
COMMENTARY hide
9054-89-1
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
physiological function
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superoxide dismutase (SOD) is a prime antioxidant enzymethat destroys the effects of superoxide, thus limiting the dele-terious effects of reactive oxygen and nitrogen species. SOD is considered an important regulator of oxida-tive/nitrosative stress
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 O2.- + 2 H+
O2 + H2O2
show the reaction diagram
2 O2.- + 2 H+ +
O2 + H2O2
show the reaction diagram
-
-
-
-
?
2 superoxide + 2 H+
O2 + H2O2
show the reaction diagram
O2- + H+
O2 + H2O2
show the reaction diagram
O2.- + H+
O2 + H2O2
show the reaction diagram
additional information
?
-
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
2 O2.- + 2 H+
O2 + H2O2
show the reaction diagram
-
-
-
-
ir
2 O2.- + 2 H+ +
O2 + H2O2
show the reaction diagram
-
-
-
-
?
2 superoxide + 2 H+
O2 + H2O2
show the reaction diagram
O2.- + H+
O2 + H2O2
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Co2+
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Co2+ binds at zinc site
copper
Cu
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a Cu,Zn superoxide dismutase
Manganese
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a MnSOD
Mn
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a Mn-SOD
Zn
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a Cu,Zn superoxide dismutase
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5,5'-dithiobis(2-nitrobenzoate)
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Mn-SOD
5-(((2,4-dichlorobenzyl)(propyl)amino)methyl)-1H-pyrazol-3(2H)-one
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EC50 value is 630 nM
5-(((3,5-dichlorobenzyl)(ethyl)amino)methyl)-1H-pyrazol-3(2H)-one
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EC50 value is 420 nM
5-(((3,5-dichlorobenzyl)(isopropyl)amino)methyl)-1H-pyrazol-3(2H)-one
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EC50 value is 0.00108 mM
5-(((3,5-dichlorobenzyl)(methyl)amino)methyl)-1H-pyrazol-3(2H)-one
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EC50 value is 480 nM
5-(((3,5-dichlorobenzyl)(propyl)amino)methyl)-1H-pyrazol-3(2H)-one
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EC50 value is 470 nM
5-(((3,5-dichlorophenethyl)(methyl)amino)methyl)-1H-pyrazol-3(2H)-one
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EC50 value is 0.00164 mM
5-(((3-(3,5-dichlorophenyl)propyl)(methyl)amino)methyl)-1H-pyrazol-3(2H)-one
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EC50 value is 0.00332 mM
5-((benzyl(3,5-dichlorobenzyl)amino)methyl)-1H-pyrazol-3(2H)-one
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EC50 value is 0.00245 mM
5-((cyclopropyl(3,5-dichlorobenzyl)amino)methyl)-1H-pyrazol-3(2H)-one
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EC50 value is 0.00134 mM
5-[(3,5-dichlorophenoxy)methyl]-1,2-dihydro-3H-pyrazol-3-one
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EC50 value is 400 nM
5-[[(3,5-dichlorophenyl)(methyl)amino]methyl]-1,2-dihydro-3H-pyrazol-3-one
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EC50 value is 570 nM
azide
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the azide ion acts as a strong competitive inhibitor for SOD by binding directly to the active site metal. Azide is bound end-on at the sixth coordinate position of the manganese ion. Tetrameric electrostatic surfaces are calculated incorporating accurate partial charges for the active site in three states, including a state with superoxide coordinated to the metal using the position of azide as a model
CN-
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extracellular enzyme
di-N-(3,5-dichlorobenzyl)-N-methyl-1-(5-oxo-2,5-dihydro-1H-pyrazol-3-yl)methanaminium sulfate
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EC50 value is 480 nM
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diethyldithiocarbamate
iodoacetamide
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Mn-SOD
Mn(Me-Phimp)2(ClO4)
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i.e. Mn(2-(1-(2-phenyl-2-(pyridine-2-yl)hydrazono)ethyl)phenol)chlorate, active as cofactor in superoxide dismutation reaction
Mn(N-Phimp)2
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i.e. Mn-(2-((2-phenyl-2-(pyridin-2-yl)hydrazono)methyl)napthalen-1-ol), active as cofactor in superoxide dismutation reaction
Mn(N-Phimp)2(ClO4)
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i.e. Mn(2-((2-phenyl-2-(pyridin-2-yl)hydrazono)methyl)napthalen-1-ol)chlorate, active as cofactor in superoxide dismutation reaction
Mn(Phimp)2
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i.e. Mn(2-((2-phenyl-2-(pyridin-2-yl)hydazono)methyl)phenol), active as cofactor in superoxide dismutation reaction
Mn(Phimp)2(ClO4)
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i.e. Mn(2-((2-phenyl-2-(pyridin-2-yl)hydazono)methyl)phenol)chlorate, active as cofactor in superoxide dismutation reaction
N-(3,5-dichlorobenzyl)-N-methyl-1-(5-oxo-2,5-dihydro-1H-pyrazol-3-yl)methanaminium chloride
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EC50 value is 510 nM
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N-(3,5-dichlorobenzyl)-N-methyl-1-(5-oxo-2,5-dihydro-1H-pyrazol-3-yl)methanaminium citrate
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EC50 value is 480 nM
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N-(3,5-dichlorobenzyl)-N-methyl-1-(5-oxo-2,5-dihydro-1H-pyrazol-3-yl)methanaminium dibasic phosphate
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EC50 value is 480 nM
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N-(3,5-dichlorobenzyl)-N-methyl-1-(5-oxo-2,5-dihydro-1H-pyrazol-3-yl)methanaminium L-tartrate
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EC50 value is 480 nM
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O2-
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substrate inhibition for mutant C140S/Q143A
Penicillamine
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copper-chelator, wild-type and mutant Cu,Zn-SOD
peroxynitrite
almost complete inhibition via nitration of active-site residue Y34, no significant change in conformation upon nitration. Inhibition occurs either through a steric effect of 3-nitrotyrosine 34 that impedes substrate binding or through an electrostatic effect of the nitro group
phenyl mercuric acetate
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Cu,Zn-SOD
Sodium dodecyl sulfate
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2% w/v, Cu,Zn-SOD and EC-SOD
additional information
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1100 - 40000
O2-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.06
O2-
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mutant C140S/Q143A, pH 9.0, 25C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00076
Mn(Me-Phimp)2(ClO4)
Homo sapiens;
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0.00112
Mn(N-Phimp)2(ClO4)
Homo sapiens;
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0.00029
Mn(Phimp)2
Homo sapiens;
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0.00039
Mn(Phimp)2(ClO4)
Homo sapiens;
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
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assay at
7.4
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assay at
7.4 - 9
assay at
7.8
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assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.4 - 10.9
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
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assay at room temperature
25
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assay at
37
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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an ovarian carcinoma cell line
Manually annotated by BRENDA team
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internal mammary arteries
Manually annotated by BRENDA team
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harbors MnSOD with the ala16val polymorphism
Manually annotated by BRENDA team
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aortic smooth muscle
Manually annotated by BRENDA team
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saphenous veins
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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MnSOD is translated in the cytoplasm and then imported into the mitochondria via a mitochondrial targeting signal
Manually annotated by BRENDA team
PDB
SCOP
CATH
UNIPROT
ORGANISM
Homo sapiens;
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
15800
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x * 15800, MALDI-TOF-MS
21300
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4 * 21300, SDS-PAGE
28000
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4 * 28000, recombinant EC-SOD, SDS-PAGE
32000
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Cu,Zn-SOD; gel filtration
35000
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dimeric wild-type holo-enzyme
38000
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2 * 38000, recombinant chimera MnSOD-VHb, SDS-PAGE
76000
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recombinant chimera MnSOD-VHb, gel filtration
additional information
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primary structure of human erythrocyte enzyme
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
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2 * 38000, recombinant chimera MnSOD-VHb, SDS-PAGE
homotetramer
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4 * 22000, Mn-SOD, SDS-PAGE
monomer
1 * 33000, recombinant enzyme, SDS-PAGE
monomer or dimer
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the kinetic mechanism for holo SODs involves native dimer-monomer intermediate, and unfolded monomer, with variable metal dissociation from the monomeric states depending on solution conditions, overview. Naturally occuring mutants seem to favour increased formation of a Zn-free monomer intermediate, which is implicated in the formation of toxic aggregates. Kinetic basis for the extremely high stability of wild-type holo SOD, overview
tetramer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
comparison of native protein and enzyme nitrated at active site residue Y34, no significant change in conformation upon nitration
crystal structures of unfluorinated and fluorinated enzyme are nearly superimposable. Ratio kcat/Km decreases from 0.8 per mM and s for wild-type to 0.03 per mM and s for the fluorinated mutant which is in significant part due to 3-fluorotyrosine residues distant from the active-site metal
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enzyme 10 mg per ml in Tris/HCl 50 mM, pH 8.2 by dialysis against ammonium sulfate 2.8 M, pH 8.2, 4C
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from recombinant Mn-SOD, asymmetric unit, hanging drop technique, room temperature, equilibration of 3-4 mg/ml enzyme in ammonium phosphate, pH 5.9, plus 10% 2-methyl-2,4-pentanediol against 32% 2-methyl-2,4-pentanediol, X-ray analysis
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mutant enzymes F66A and F66L, hanging drop vapor diffusion method, 0.005 ml of enzyme solution are mixed with 0.005 ml of precipitant solution containing 2.5 M ammonium sulfate, 100 mM imidazole, and 100 mM malic acid, pH 8.5, equilibration against 1 ml of precipitant solution, 1 week, room temperature, X-ray diffraction structure determination and analysis at 2.2 A and 2.3 A resolution, respectively
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purified enzyme MnSOD in complex with azide, hanging-drop vapor diffusion, mixing of 0.001 ml of 21 mg/ml protein solution with 0.001 ml of reservoir solution 1.8 M potassium phosphate, pH 7.8, at room temperature for1 day, to obtain the azide complex, 0.002 ml of reservoir containing 200 mM sodium azide are added to drops of 6 day crystals, X-ray diffraction structure determination and analysis at 1.77-1.82 A resolution
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purified recombinant SOD1, hanging drop vapour diffusion, 0.001 ml of 10 mg/ml protein in 50 mM sodium citrate, pH 5.5, 1 mM DTT, 100 mM CuSO4, and 100 mM ZnSO4, is mixed with 0.001 ml of reservoir solution containing 21-25% w/v PEG 4000, 0.1 M sodium acetate, pH 4.2-5.2, X-ray diffraction structure determination and analysis at 3.5 A, molecular replacement
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purified zinc-deficient mutant enzyme, 0.002 ml of solution containing 15.7 mg/ml protein in 50 mM Na/K phosphate, pH 7.7, is mixed with 0.002 ml of reservoir solution containing 2.45 M ammonium sulfate, 200 mM NaCl in 50 mM Tris, pH 7.5, room temperature, less than 1 week, X-ray diffraction structure determination and analysis at 2.0 A resolution, modelling
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recombinant human Cu,Zn-SOD expressed in yeast, hanging drop method by vapour diffusion from 50 mM phosphate, pH 7.7, resulting in 3 different crystal forms
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wild-type, beta-barrel mutant H43R, dimer interface mutant A4V
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5
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5C, 1 day, 35% loss of activity
438120
7.2
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4C, 1 day, 2% loss of activity
438120
8 - 9.3
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4C, 1 day, 10-20% loss of activity
438120
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
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wild-type, purified stable for at least 1 week
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
SDS, 1%, complete loss of activity after 6 h
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urea: 8 M, stable
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ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
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Mn-SOD and Fe-SOD: not stable to organic solvents, Cu,Zn-SOD: stable to organic solvents
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-35C, protein concentration 45 mg/ml, 50% glycerol
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cu,Zn-SOD from erythrocytes
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Cu,Zn-SOD from erythrocytes; Cu,Zn-SOD from liver; Mn-SOD from liver
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Cu,Zn-SOD wild-type and mutant recombinant from Escherichia coli
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Cu,Zn-SOD, wild-type and mutants recombinant from Spodoptera frugiperda cells
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Cu,Zn-SOD; extracellular; Mn-SOD from liver
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EC-SOD from aorta
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EC-SOD recombinant from Escherichia coli as His-tagged protein and partially from insect cells
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large scale immunoisolation of native mutant and wildtype SOD1
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Mn-SOD from liver
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recombinant chimera MnSOD-VHb from Escherichia coli strain BL21(DE3)
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recombinant Cu,Zn-SOD
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recombinant SOD1 from Leishmania tarentolae strain P10 to 90% purity by ultracentrifugation, hydrophobic interaction chromatography and dialysis
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recombinant wild-type and truncated mutant FLAG-tagged hEC-SOD enzymes from Spodoptera frugiperda Sf9 cells by affinity chromatography
soluble recombinant enzyme SOD2 from Escherichia coli cell-free extract by dialysis, anion exchange chromatography, again dialysis, and ultrafiltration
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cu,Zn-SOD, expression of wild-type and mutant in Escherichia coli
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Cu,Zn-SOD, overexpression in Escherichia coli
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Cu,Zn-SOD, overexpression of wild-type and mutants in Spodoptera frugiperda cells Sf21 via baculovirus infection
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DNA and amino acid sequence determination and analysis, ala16val polymorphism genotyping, overview, stably expression of human MnSOD-A16 and MnSOD-V16 variants in mouse fibroblasts
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EC-SOD, overexpression in Escherichia coli as His-tagged protein and in Tn-5B1-4 cells of Trichoplusia ni via baculovirus infection
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expression in yeast
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expression of H63C mutant in Escherichia coli
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expression of human SOD in Escherichia coli
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expression of recombinant chimera MnSOD-VHb in Escherichia coli strain BL21(DE3)
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expression of SOD1 in Leishmania tarentolae strain P10
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expression of the CuZn-SOD in Escherichia coli
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expression of wild-type and mutant enzymes in Escherichia coli
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gene sod, expression of wild-type and mutant soluble enzymes in Escherichia coli strain QC774, that lacks the genes encoding endogeneous FeSOD, SodB-, and MnSOD, SodA-
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gene sod-1, expression analysis
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gene SOD2, recombinant expression in Escherichia coli
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gene SOD3, cloning of EC-SOD and recombinant expression of wild-type and truncated mutant FLAG-tagged hEC-SOD enzymes in Spodoptera frugiperda Sf9 cells using the baculovirus transfection method, both full length and truncated hEC-SOD proteins are enzymatically active
Mn-SOD, expression in Escherichia coli
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overexpression of wild-type and mutant enzymes in hind limb muscle of transgenic mice
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
docosahexaenoic acid inhibits enzyme transcription in cancer cells, involvement of hypoxia-inducible factor-2alpha signaling, but not of peroxisome proliferator-activated receptor alpha, overview. Suppression of SOD-1 expression by clofibrate also requires hypoxia-inducible factor-2alpha and the binding element in the SOD-1 promoter
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A16V
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naturally occuring ala16val polymorphism genotyping, overview
A4V
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mutation causing familial amyotrophic lateral scerosis, 30% of wild-type activity, 1.06 atoms of copper and 1.43 atoms of zinc per subunit
C111S
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site-directed mutagenesis, the mutant has 1.07 copper and 1.18 zinc per subunit
C140S
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catalytic efficiency similar to wild-type, product inhibition is less than in wild-type
C140S/Q143A
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catalysis does not follow Michaelis-Menten kinetics, substrate inhibition with KI-value of 0.06 mM
D124N
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site-directed mutagenesis, the mutant has 0.93 copper and 0.03 zinc per subunit
D124N/C111S
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site-directed mutagenesis, the mutant has 0.93 copper and 0.03 zinc per subunit
D83S
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site-directed mutagenesis, the mutant has 0.93 copper and 0.08 zinc per subunit
D83S/C111S
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site-directed mutagenesis, the mutant has 0.93 copper and 0.08 zinc per subunit
E100G
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an amyotrophic lateral sclerosis-associated naturally occuring SOD mutant, misfolding/aggregation mechanism with folding and unfolding kinetics, overview
E93A
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construction of transgenic mice overexpressing wild-type and mutant SOD1, biochemical changes occur in the hindlimb muscle of young, presymptomatic G93A hSOD1 transgenic mice, cdk5 activity is reduced in hindlimb muscle of 27-day-old G93A hSOD1 transgenic mice by suppression through the mutant E93A enzyme, phenotype, overview, mutant G93A SOD1 also suppresses muscle cdk5 activity in vitro
F50E/G51E
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about 20% of wild-type activity, monomeric
F66A
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site-directed mutagenesis, alteration of the active site surrounding, the mutant is 3fold less sensitive to product inhibition compared to the wild-type enzyme
F66L
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site-directed mutagenesis, alteration of the active site surrounding, the mutant shows residual product inhibition with formation of a peroxide-inhibited enzyme and increased catalytic activity
G41N
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Cu,Zn-SOD, site-directed mutagenesis, analogous to mutant found in familial amyotrophic lateral sclerosis, 47% activity compared to the wild-type
G93R
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an amyotrophic lateral sclerosis-associated naturally occuring SOD mutant, misfolding/aggregation mechanism with folding and unfolding kinetics, overview
H46R
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an amyotrophic lateral sclerosis-associated naturally occuring SOD mutant, misfolding/aggregation mechanism with folding and unfolding kinetics, overview
H63C
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Cu,Zn-SOD, mutant with exchange of metal-bridging proton-donor His63 for Cys, binds Cu2+, but not Zn2+, 1% remaining activity compared to wild-type
H80S/D83S
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site-directed mutagenesis, the mutant has 0.93 copper and 0.08 zinc per subunit
H80S/D83S/C6A/C111S
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site-directed mutagenesis, the mutant has 1.07 copper and 1.18 zinc per subunit
N73S
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ratio kcat/Km about twofold smaller than in wild-type, product inhibition similar to wild-type
N73S/C140S/Q143A
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catalytic efficiency much smaller than wild-type, no appreciable product inhibition
N73S/Q143A
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catalytic efficiency much smaller than wild-type, no appreciable product inhibition
Q143A
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dramatically reduced product inhibition, reduced catalytic activity and efficiency
Y34F
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about 12fold decrease in kcat value
additional information
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
apoprotein expressed in insect cells can be restored by addition of Cu2+, fully active
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enzyme folding and unfolding kinetic mechanism of wild-type and mutant enzymes at pH 7.8 and 25C, role of metal ions, overview
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recombinant EC-SOD refolds from inclusion bodies in E. coli after denaturing
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
synthesis