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Information on EC 1.17.3.2 - xanthine oxidase and Organism(s) Rattus norvegicus and UniProt Accession P22985

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EC Tree
     1 Oxidoreductases
         1.17 Acting on CH or CH2 groups
             1.17.3 With oxygen as acceptor
                1.17.3.2 xanthine oxidase
IUBMB Comments
An iron-molybdenum flavoprotein (FAD) containing [2Fe-2S] centres. Also oxidizes hypoxanthine, some other purines and pterins, and aldehydes, but is distinct from EC 1.2.3.1, aldehyde oxidase. Under some conditions the product is mainly superoxide rather than peroxide: RH + H2O + 2 O2 = ROH + 2 O2.- + 2 H+. The mammalian enzyme predominantly exists as an NAD-dependent dehydrogenase (EC 1.17.1.4, xanthine dehydrogenase). During purification the enzyme is largely converted to the O2-dependent xanthine oxidase form (EC 1.17.3.2). The conversion can be triggered by several mechanisms, including the oxidation of cysteine thiols to form disulfide bonds [4,5,7,10] [which can be catalysed by EC 1.8.4.7, enzyme-thiol transhydrogenase (glutathione-disulfide) in the presence of glutathione disulfide] or limited proteolysis, which results in irreversible conversion. The conversion can also occur in vivo [4,6,10].
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UNIPROT: P22985
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Word Map
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Synonyms
xo, hypoxanthine-xanthine oxidase, xanthine:xanthine oxidase, xanthine:oxygen oxidoreductase, xanthine oxygen oxidoreductase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
xanthine dehydrogenase/oxidase
UniProt
xanthine oxidoreductase
-
hypoxanthine oxidase
-
-
-
-
hypoxanthine-xanthine oxidase
-
-
-
-
hypoxanthine:oxygen oxidoreductase
-
-
-
-
oxidase, xanthine
-
-
-
-
Schardinger enzyme
-
-
-
-
xanthine oxidoreductase
xanthine:O2 oxidoreductase
-
-
-
-
xanthine:xanthine oxidase
-
-
-
-
additional information
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
xanthine + H2O + O2 = urate + H2O2
show the reaction diagram
reaction mechanism of XOR and binding modes of the substrate xanthine, overview. The oxidative hydroxylation of purine substrates takes place at the molybdenum center. Reducing equivalents introduced there are then transferred via two [2Fe-2S] centers to the FAD cofactor where reduction of the physiological electron acceptors occurs, NAD+ in the case of the dehydrogenase form, XDH, or O2 in the oxidase form, XO, of the enzyme occur
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
xanthine:oxygen oxidoreductase
An iron-molybdenum flavoprotein (FAD) containing [2Fe-2S] centres. Also oxidizes hypoxanthine, some other purines and pterins, and aldehydes, but is distinct from EC 1.2.3.1, aldehyde oxidase. Under some conditions the product is mainly superoxide rather than peroxide: RH + H2O + 2 O2 = ROH + 2 O2.- + 2 H+. The mammalian enzyme predominantly exists as an NAD-dependent dehydrogenase (EC 1.17.1.4, xanthine dehydrogenase). During purification the enzyme is largely converted to the O2-dependent xanthine oxidase form (EC 1.17.3.2). The conversion can be triggered by several mechanisms, including the oxidation of cysteine thiols to form disulfide bonds [4,5,7,10] [which can be catalysed by EC 1.8.4.7, enzyme-thiol transhydrogenase (glutathione-disulfide) in the presence of glutathione disulfide] or limited proteolysis, which results in irreversible conversion. The conversion can also occur in vivo [4,6,10].
CAS REGISTRY NUMBER
COMMENTARY hide
9002-17-9
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
hypoxanthine + 2 H2O + 2 O2
urate + 2 H2O2
show the reaction diagram
-
-
-
?
xanthine + H2O + O2
urate + H2O2
show the reaction diagram
allopurinol + H2O + O2
oxypurinol + H2O2
show the reaction diagram
-
allopurinol is a substrate and a competitive inhibitor for xanthine oxidase, it binds irreversibly at the active site reducing molybdenum VI to IV
-
-
?
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
show the reaction diagram
-
enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
-
-
?
hypoxanthine + 2 H2O + 2 O2
urate + 2 H2O2
show the reaction diagram
pteridine + H2O + O2
?
show the reaction diagram
-
-
-
-
?
purine + H2O + O2
?
show the reaction diagram
-
-
-
-
?
xanthine + H2O + O2
urate + H2O2
show the reaction diagram
xanthine + H2O + O2
uric acid + H2O2
show the reaction diagram
xanthine + O2 + H2O
urate + H2O2
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
hypoxanthine + 2 H2O + 2 O2
urate + 2 H2O2
show the reaction diagram
-
-
-
?
xanthine + H2O + O2
urate + H2O2
show the reaction diagram
carboxylic aldehyde + H2O + O2
carboxylic acid + H2O2
show the reaction diagram
-
enzyme is implicated in the control of various redox reactions in the cell, in milk: assures absorption of iron from the gut, coupling antibacterial effect via the lactoperoxidase system
-
-
?
pteridine + H2O + O2
?
show the reaction diagram
-
-
-
-
?
purine + H2O + O2
?
show the reaction diagram
-
-
-
-
?
xanthine + H2O + O2
urate + H2O2
show the reaction diagram
xanthine + O2 + H2O
urate + H2O2
show the reaction diagram
-
-
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
molybdenum cofactor
cofactor geometry, overview
molybdopterin
one molybdopterin per enzyme molecule
[2Fe-2S]-center
two nonidentical [2Fe-2S] clusters designated as Fe/SI and Fe/SII, distinguished by redox potential and EPR signal
molybdenum cofactor
additional information
cofactor conformation, binding structure analysis and mechanism, overview
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Iron
two [2Fe-2S] centers
Molybdenum
Iron
-
iron-molybdenum protein
Mo
-
XOR is a molybdenum-containing enzyme
Molybdenum
-
an iron-molybdenum protein
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-[3-cyano-4-(2,2-dimethylpropoxy)phenyl]-1H-pyrazole-4-carboxylic acid
-
-
2-Amino-4-hydroxy-6-formylpterine
-
-
2-[(2,3-dimethylphenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
-
-
2-[(2,4-dimethylphenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
-
-
2-[(2-bromophenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
-
-
2-[(2-chlorophenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
-
-
2-[(2-fluorophenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
-
-
2-[(3-bromophenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
-
-
2-[(3-chlorophenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
-
-
2-[(3-fluorophenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
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-
2-[(4-bromophenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
-
-
2-[(4-chloro-3-methylphenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
-
-
2-[(4-chlorophenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
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-
2-[(4-fluorophenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
-
-
2-[(4-methoxyphenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
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7-methyl-2-(phenoxymethyl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
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7-methyl-2-[(2-methylphenoxy)methyl]-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
-
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7-methyl-2-[(2-nitrophenoxy)methyl]-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
-
-
7-methyl-2-[(3-methylphenoxy)methyl]-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
-
-
7-methyl-2-[(3-nitrophenoxy)methyl]-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
-
-
7-methyl-2-[(4-methylphenoxy)methyl]-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
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7-methyl-2-[(4-nitrophenoxy)methyl]-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
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8-Hydroxyquinoline-7-sulfonic acid
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-
allopurinol
apigenin
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-
arsenite
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ascorbic acid
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asperuloside
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from Paederia scandens extract
chalcones
-
-
epicatechin
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-
febuxostat
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the inhibitor lowers uric acid and alleviates systemic and glomerular hypertension in experimental hyperuricaemia
green tea extract
-
-
-
hesperetin
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i.e. 3',5,7-trihydroxy-4'-methoxyflavanone, major flavanone component of orange juice, inhibits hepatic XOR activity and decreases serum uric acid levels, exhibits antioxidative and antihyperuricemic properties
hydroxylamine
-
-
Imidazotriazines
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lithospermic acid
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isolated from roots of medicinal herb Salvia mitiorrhiza, the compound shows competitive enzyme inhibition activity and in vivo hypouricemic and anti-inflammatory effects in rats pretreated with uricase inhibitor potassium oxonate, overview
luteolin
-
-
ninhydrin
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orange juice
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inhibits hepatic XOR activity and decreases serum uric acid levels and exhibits antioxidative and antihyperuricemic properties
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oxypurinol
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p-chloromercuribenzoate
-
-
paederoside
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from Paederia scandens extract
pycnogenol
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extract from french maritime pine bark, contains 75% (w/w) procyanidins formed by catechin and epicatechin but also taxifolin and phenolcarbonic acids and their glycosides, uncompetitive inhibitor, 0.01 mg/ml, 35% inhibition, 0.1 mg/ml, 80% inhibition, enzyme recovers activity upon dissociation of pycnogenol from enzyme
-
Pyridine
-
highly reduced activity of xanthine oxidase in the presence of pyridine, overview
quercetin
-
-
scandoside
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from Paederia scandens extract
Tetraethylthiuram disulfide
-
-
Tungsten
-
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
potassium oxonate
-
slight activation in vivo
Th-1 cytokine
-
increases XOR activity in inflammatory mononuclear phagocytes in vivo
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0497 - 0.129
O2
0.0018 - 0.002
xanthine
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.41 - 12.47
xanthine
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00176
2-[(2,4-dimethylphenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
Rattus norvegicus
-
pH 7.5, temperature not specified in the publication
0.000413
2-[(2-bromophenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
Rattus norvegicus
-
pH 7.5, temperature not specified in the publication
0.000183
2-[(2-chlorophenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
Rattus norvegicus
-
pH 7.5, temperature not specified in the publication
0.00059
2-[(2-fluorophenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
Rattus norvegicus
-
pH 7.5, temperature not specified in the publication
0.00256
2-[(3-bromophenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
Rattus norvegicus
-
pH 7.5, temperature not specified in the publication
0.00618
2-[(3-chlorophenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
Rattus norvegicus
-
pH 7.5, temperature not specified in the publication
0.00198
2-[(3-fluorophenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
Rattus norvegicus
-
pH 7.5, temperature not specified in the publication
0.000623
2-[(4-chloro-3-methylphenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
Rattus norvegicus
-
pH 7.5, temperature not specified in the publication
0.000449
2-[(4-chlorophenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
Rattus norvegicus
-
pH 7.5, temperature not specified in the publication
0.000289
2-[(4-methoxyphenoxy)methyl]-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
Rattus norvegicus
-
pH 7.5, temperature not specified in the publication
0.000555
7-methyl-2-(phenoxymethyl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
Rattus norvegicus
-
pH 7.5, temperature not specified in the publication
0.000362
7-methyl-2-[(2-methylphenoxy)methyl]-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
Rattus norvegicus
-
pH 7.5, temperature not specified in the publication
0.00107
7-methyl-2-[(3-methylphenoxy)methyl]-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
Rattus norvegicus
-
pH 7.5, temperature not specified in the publication
0.00102
7-methyl-2-[(4-methylphenoxy)methyl]-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
Rattus norvegicus
-
pH 7.5, temperature not specified in the publication
0.00203
7-methyl-2-[(4-nitrophenoxy)methyl]-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one
Rattus norvegicus
-
pH 7.5, temperature not specified in the publication
0.000753
allopurinol
Rattus norvegicus
-
pH 7.5, temperature not specified in the publication
additional information
additional information
Rattus norvegicus
-
IC50 of lithopsermic acid is 0.0052 mg/ml
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.003
-
crude, cell-free liver enzyme extract
189.6
-
electron acceptor O2
800
-
electron acceptors O2 and NAD+
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
23
-
assay at
37
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
lower enzyme activity compared to vena cava
Manually annotated by BRENDA team
higher enzyme activity compared to aorta
Manually annotated by BRENDA team
-
enzyme activity in intestinal tissues in experimental sepsis, overview
Manually annotated by BRENDA team
-
alveolar macrophages purified from the lung by lavage, and interstitial macrophages. Inflammatory cells express high levels of XOR activity, while in resident alveolar macrophage the enzyme content is extremely low prior to cytokine insufflation
Manually annotated by BRENDA team
-
after weaning, during the involution of the mammary gland, enzyme activity increases and high mitochondrial H2O2 production takes place. Inhibition of xanthine oxidase slows down the involution of the mammary gland due to the decrease in the number of apoptotic cells and prevents the production of H2O2 that occurs during apoptosis
Manually annotated by BRENDA team
-
positive correlation between plasma xanthine oxidase activity and expression and age of the animal
Manually annotated by BRENDA team
-
positive correlation between plasma xanthine oxidase activity and expression and age of the animal
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
matrix and core of peroxisomes of liver parenchymal cells, xanthine oxidoreductase and xanthine oxidase detected
Manually annotated by BRENDA team
additional information
-
only XOR activity is present in the cytoplasm of rat liver parenchymal cells. In Kupffer cells and sinusoidal endothelial cell xanthine oxidoreductase activity is demonstrated in vesicles and occasionally on granular endoplasmic reticulum. Xanthine oxidase activity is not found in Kupffer cells and sinusoidal cells
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
mammalian xanthine oxidoreductase can exist in both dehydrogenase and oxidase forms. The C-terminal peptide plays a role in the formation of an intermediate form during the transition between xanthine dehydrogenase and xanthine oxidase. Conversion between the two is implicated in such diverse processes as lactation, anti-bacterial activity, reperfusion injury and a growing number of diseases. The dehydrogenase-oxidase transformation occurs rather readily and the insertion of the C-terminal peptide into the active site cavity of its subunit stabilizes the dehydrogenase form. The intermediate form can be generated (e.g. in endothelial cells) upon interaction of the C-terminal peptide portion of the enzyme with other proteins or the cell membrane. Residues Cys535 and Cys992 are involved in the rapid phase and Cys1316 and Cys1324 in the slow phase of the modification reaction. The irreversible conversion of XDH to XOR by trypsin involves limited proteolysis at the same linker peptide. Triggering events, such as the formation of a disulfide bond between Cys535 and Cys992 or proteolysis of the linker, reorient Phe549 (also a part of the long linker), resulting in disruption of a four amino acid cluster. Arg426 is then released from the cluster and moves the A-loop that blocks the approach of NAD+ to the flavin ring of the FAD moiety, as well as changing the electrostatic environment
metabolism
-
effects of enzyme inhibition in inflammatory macrophages, overview
physiological function
-
xanthine oxidoreductase catalyzes the oxidation of hypoxanthine to xanthine or xanthine to uric acid in the metabolic pathway of purine degradation
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
XDH_RAT
1331
0
146243
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
-
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 150000, about, C-terminally truncated mutant enzyme DELTAC, SDS-PAGE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
-
-
additional information
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant C-terminally truncated mutant enzyme, crystals of the mutant protein are prepared in two ways: (a) crystallization of the protein directly after DTT treatment and (b) crystallization in the presence of DTT followed by extended soaks in mother liquor devoid of DTT to convert most of the protein to the XO form, X-ray diffraction structure determination and analysis at 2.0 A resolution. Comparisons of crystal structures of a stable wild-type XDH enzyme form, the triple mutant C535A/C992R/C1324, and the DELTAC truncated mutant XOR
xanthine oxidoreductase mutant W335A/F336L, showing two similar, but not identical subunits. The cluster involved in conformation-switching is completely disrupted in one subunit, but remains partly associated in the other. Xanthine oxidase and oxidoreductase forms of the mutant are in equilibrium that greatly favors the oxidase form, but upon incubation with dithiothreitol equilibrium is partly shifted towards the oxidoreductase form
XOR complexed with the artificial substrate 4-[5-pyridine-4-yl-1H-[1,2,4]triazol-3-yl]pyridine-2-carbonitril, FYX-051, crystal structure analysis. Urate complexes of the purified recombinant demolybdo-form of mutant D428A, X-ray diffraction structure determination and analysis at 1.7 A resolution
W335A/F336L double mutant enzyme crystal structure analysis
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C535A/C992R
site-directed mutagenesis, the mutant activity in the presence of sulfhydryl residue modifiers is very low
C535A/C992R/C1316S
site-directed mutagenesis, the triple mutant does not undergo conversion from XOR, EC 1.17.3.2, to XDH, EC 1.17.1.4, at all
C535A/C992R/C1324S
site-directed mutagenesis, the triple mutant does not undergo conversion from XOR, EC 1.17.3.2, to XDH, EC 1.17.1.4, at all
W335A/F336L
xanthine oxidoreductase mutant displaying xanthine oxidase activity
W335A/F336L
-
xanthine oxidase locked mutant
additional information
construction of a variant of the rat liver enzyme that lacks the C-terminal amino acids 1316-1331. The mutant enzymes appears to assume an intermediate form, exhibiting a mixture of dehydrogenase and oxidase activities. The purified mutant protein retains about 50-70% of oxidase activity even after prolonged dithiothreitol treatment. The C-terminal region plays a role in the dehydrogenase to oxidase conversion. In the crystal structure of the protein variant, most of the enzyme stays in an oxidase conformation. But after 15 min of incubation with a high concentration of NADH, the corresponding X-ray structures show a dehydrogenase-type conformation. On the other hand, disulfide formation between Cys535 and Cys992, which can clearly be seen in the electron density map of the crystal structure of the mutant after removal of dithiothreitol, goes in parallel with the complete conversion to oxidase, resulting in structural changes identical to those observed upon proteolytic cleavage of the linker peptide
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.8
-
5°C or 10°C, 6 months, no significant loss of activity
390370
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
the thermostability of xanthine oxidase in the presence of pyridine is highly increased compared to the unbound enzyme, overview
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
rat liver enzyme is unstable as dehydrogenase and is gradually converted to oxidase
-
the enzyme from animal tissues can be interconverted to EC 1.1.1.204, that from liver exists in vivo mainly as the dehydrogenase form, but can be converted into the oxidase form by storage at -20°C, by treatment with proteolytic enzymes or with organic solvents, or by thiol reagents such as Cu2+, N-ethylmaleimide or 4-hydroxymercuribenzoate, the effect of the thiol reagents can be reversed by thiols such as 1,4-dithioerythritol, in other animal tissues the enzyme exists almost entirely as EC 1.1.3.22 but can be converted into the dehydrogenase form by 1,4-dithioerythritol
-
the xanthine dehydrogenase form can be obtained through incubation of xanthine oxidase with sulfhydryl reducing reagents
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate, hydroxyapatite, DEAE-cellulose
-
from liver
-
simultaneous purification of xanthine oxidase and aldehyde oxidase
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of enzyme mutant D428A in Spodoptera frugiperda Sf9 cells via the baculovirus transfection system in mostly the demolybdo-form
ectopic overexpression of XOR cDNA and uric acid supplementation reducing SUMO-PPARgamma in inflammatory mononuclear phagocytes
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pharmacology
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inhibition of xanthine oxidase is a potential therapeutic approach to diabetic neuropathy and vasculopathy
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Maia, L.; Mira, L.
Xanthine oxidase and aldehyde oxidase: A simple procedure for the simultaneous purification from rat liver
Arch. Biochem. Biophys.
400
48-53
2002
Rattus norvegicus
Manually annotated by BRENDA team
Waud, W.R.; Rajagopalan, K.V.
Purification and properties of the NAD+-dependent (type D) and O2-dependent (type O) forms of rat liver xanthine dehydrogenase
Arch. Biochem. Biophys.
172
354-364
1976
Rattus norvegicus
Manually annotated by BRENDA team
Della Corte, E.; Stirpe, F.
The regulation of rat liver xanthine oxidase. Involvement of thiol groups in the conversion of the enzyme activity from dehydrogenase (type D) into oxidase (type O) and purification of the enzyme
Biochem. J.
126
739-745
1972
Rattus norvegicus
Manually annotated by BRENDA team
Moini, H.; Guo, Q.; Packer, L.
Enzyme inhibiton and protein-binding action of the procyanidin-rich french maritime pine bark extract, pycnogenol: effect on xanthine oxidase
J. Agric. Food Chem.
48
5630-5639
2000
Rattus norvegicus
Manually annotated by BRENDA team
Zikakis, J.P.; Dressel, M.A.; Silver, M.R.
Bovine, caprine, and human milk xanthine oxidases: isolation, purification, and characterization
Instrum. Anal. Foods, Recent Prog. (Proc. Symp. Int. Flavor Conf. , 3rd Ed. , Charalambous, G. , Inglett, G. , eds. )
2
243-303
1983
Bos taurus, Canis lupus familiaris, Capra hircus, Cavia porcellus, Oryctolagus cuniculus, Equus asinus, Equus caballus, Erythrocebus patas, Felis catus, Ovis aries, Homo sapiens, Mus musculus, Rattus norvegicus, Erythrocebus patas Patas monkey
-
Manually annotated by BRENDA team
Stirpe, F.; Della Corte, E.
The regulation of rat liver xanthine oxidase: conversion of type D (dehydrogenase) into type O (oxidase) by a thermolabile factor, and reversibility by dithioerythritol
Biochim. Biophys. Acta
212
195-197
1970
Bos taurus, Rattus norvegicus
Manually annotated by BRENDA team
De Renzo, E.C.
Chemistry and biochemistry of xanthine oxidase
Adv. Enzymol. Relat. Subj. Biochem.
17
293-328
1956
Bos taurus, Gallus gallus, Rattus norvegicus
Manually annotated by BRENDA team
Frederiks, W.M.; Vreeling-Sindelarova, H.
Ultrastructural localization of xanthine oxidoreductase activity in isolated rat liver cells
Acta Histochem.
104
29-37
2002
Rattus norvegicus
Manually annotated by BRENDA team
Rus, D.A.; Sastre, J.; Vina, J.; Pallardo, F.V.
Induction of mitochondrial xanthine oxidase activity during apoptosis in the rat mammary gland
Front. Biosci.
12
1184-1189
2007
Rattus norvegicus
Manually annotated by BRENDA team
Asai, R.; Nishino, T.; Matsumura, T.; Okamoto, K.; Igarashi, K.; Pai, E.F.; Nishino, T.
Two mutations convert mammalian xanthine oxidoreductase to highly superoxide-productive xanthine oxidase
J. Biochem.
141
525-534
2007
Rattus norvegicus (P22985)
Manually annotated by BRENDA team
Szasz, T.; Thompson, J.M.; Watts, S.W.
A comparison of reactive oxygen species metabolism in the rat aorta and vena cava: focus on xanthine oxidase
Am. J. Physiol. Heart Circ. Physiol.
295
H1341-H1350
2008
Rattus norvegicus (P22985)
Manually annotated by BRENDA team
George, J.; Struthers, A.D.
The role of urate and xanthine oxidase inhibitors in cardiovascular disease
Cardiovasc. Ther.
26
59-64
2008
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Liu, X.; Chen, R.; Shang, Y.; Jiao, B.; Huang, C.
Lithospermic acid as a novel xanthine oxidase inhibitor has anti-inflammatory and hypouricemic effects in rats
Chem. Biol. Interact.
176
137-142
2008
Rattus norvegicus
Manually annotated by BRENDA team
Inkster, M.E.; Cotter, M.A.; Cameron, N.E.
Treatment with the xanthine oxidase inhibitor, allopurinol, improves nerve and vascular function in diabetic rats
Eur. J. Pharmacol.
561
63-71
2007
Rattus norvegicus
Manually annotated by BRENDA team
Aranda, R.; Domenech, E.; Rus, A.D.; Real, J.T.; Sastre, J.; Vina, J.; Pallardo, F.V.
Age-related increase in xanthine oxidase activity in human plasma and rat tissues
Free Radic. Res.
41
1195-1200
2007
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Ohta, Y.; Matsura, T.; Kitagawa, A.; Tokunaga, K.; Yamada, K.
Xanthine oxidase-derived reactive oxygen species contribute to the development of D-galactosamine-induced liver injury in rats
Free Radic. Res.
41
135-144
2007
Rattus norvegicus
Manually annotated by BRENDA team
Devrim, E.; Avci, A.; Ergueder, I.B.; Karagenc, N.; Kuelah, B.; Durak, I.
Activities of xanthine oxidase and superoxide dismutase enzymes in rat intestinal tissues in sepsis
J. Trauma
64
733-735
2008
Rattus norvegicus
Manually annotated by BRENDA team
Sanchez-Lozada, L.G.; Tapia, E.; Soto, V.; Avila-Casado, C.; Franco, M.; Zhao, L.; Johnson, R.J.
Treatment with the xanthine oxidase inhibitor febuxostat lowers uric acid and alleviates systemic and glomerular hypertension in experimental hyperuricaemia
Nephrol. Dial. Transplant.
23
1179-1185
2008
Rattus norvegicus
Manually annotated by BRENDA team
Yan, H.; Ma, Y.; Liu, M.; Zhou, L.
The dual actions of Paederia scandens extract as a hypouricemic agent: xanthine oxidase inhibitory activity and uricosuric effect
Planta Med.
74
1345-1350
2008
Rattus norvegicus
Manually annotated by BRENDA team
Soucy, K.G.; Lim, H.K.; Benjo, A.; Santhanam, L.; Ryoo, S.; Shoukas, A.A.; Vazquez, M.E.; Berkowitz, D.E.
Single exposure gamma-irradiation amplifies xanthine oxidase activity and induces endothelial dysfunction in rat aorta
Radiat. Environ. Biophys.
46
179-186
2007
Rattus norvegicus
Manually annotated by BRENDA team
Mittal, A.; Phillips, A.R.; Loveday, B.; Windsor, J.A.
The potential role for xanthine oxidase inhibition in major intra-abdominal surgery
World J. Surg.
32
288-295
2008
Felis silvestris, Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Nishino, T.; Okamoto, K.; Eger, B.T.; Pai, E.F.; Nishino, T.
Mammalian xanthine oxidoreductase - mechanism of transition from xanthine dehydrogenase to xanthine oxidase
FEBS J.
275
3278-3289
2008
Bos taurus, Rattus norvegicus
Manually annotated by BRENDA team
Haidari, F.; Ali Keshavarz, S.; Reza Rashidi, M.; Mohammad Shahi, M.
Orange juice and hesperetin supplementation to hyperuricemic rats alter oxidative stress markers and xanthine oxidoreductase activity
J. Clin. Biochem. Nutr.
45
285-291
2009
Rattus norvegicus
Manually annotated by BRENDA team
Sathisha, K.R.; Khanum, S.A.; Chandra, J.N.; Ayisha, F.; Balaji, S.; Marathe, G.K.; Gopal, S.; Rangappa, K.S.
Synthesis and xanthine oxidase inhibitory activity of 7-methyl-2-(phenoxymethyl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one derivatives
Bioorg. Med. Chem.
19
211-220
2011
Bos taurus, Rattus norvegicus
Manually annotated by BRENDA team
Amini, K.; Sorouraddin, M.; Rashidi, M.
Activity and stability of rat liver xanthine oxidase in the presence of pyridine
Can. J. Chem.
89
1-7
2011
Rattus norvegicus
-
Manually annotated by BRENDA team
Okamoto, K.; Kawaguchi, Y.; Eger, B.; Pai, E.; Nishino, T.
Crystal structures of urate bound form of xanthine oxidoreductase: Substrate orientation and structure of the key reaction intermediate
J. Am. Chem. Soc.
132
17080-17083
2010
Bos taurus, Rattus norvegicus (P22985)
Manually annotated by BRENDA team
Gibbings, S.; Elkins, N.D.; Fitzgerald, H.; Tiao, J.; Weyman, M.E.; Shibao, G.; Fini, M.A.; Wright, R.M.
Xanthine oxidoreductase promotes the inflammatory state of mononuclear phagocytes through effects on chemokine expression, peroxisome proliferator-activated receptor-gamma sumoylation, and HIF-1alpha
J. Biol. Chem.
286
961-975
2011
Rattus norvegicus, Rattus norvegicus Sprague-Dawley
Manually annotated by BRENDA team
Nishino, T.; Okamoto, K.; Kawaguchi, Y.; Matsumura, T.; Eger, B.T.; Pai, E.F.; Nishino, T.
The C-terminal peptide plays a role in the formation of an intermediate form during the transition between xanthine dehydrogenase and xanthine oxidase
FEBS J.
282
3075-3090
2015
Rattus norvegicus (P22985)
Manually annotated by BRENDA team