Information on EC 1.13.99.1 - inositol oxygenase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY hide
1.13.99.1
-
RECOMMENDED NAME
GeneOntology No.
inositol oxygenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
myo-Inositol + O2 = D-glucuronate + H2O
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C-H bond cleavage
dehydrogenation
-
-
hydroxylation
-
-
oxidation
-
four-electron oxidation of myo-inositol to D-glucuronate
redox reaction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Ascorbate and aldarate metabolism
-
-
Inositol phosphate metabolism
-
-
UDP-alpha-D-glucuronate biosynthesis (from myo-inositol)
-
-
SYSTEMATIC NAME
IUBMB Comments
myo-Inositol:oxygen oxidoreductase
An iron protein.
CAS REGISTRY NUMBER
COMMENTARY hide
9029-59-8
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
-
MIOX is the first and rate-limiting enzyme in myo-inositol metabolism pathway
physiological function
additional information
-
increase in MIOX enzyme activity is in proportion to serum glucose concentrations and may be responsible for the myo-inositol depletion found in the type I diabetes mellitus complications, detailed phenotype analysis of 130 Caucasian patients, overview
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
D-chiro-inositol + O2
?
show the reaction diagram
-
-
-
-
?
D-chiro-inositol + O2
D-glucuronate
show the reaction diagram
much less active with D-chiro-inositol than with myo-inositol
-
-
-
myo-inositol + H2O
D-glucuronate + H2O
show the reaction diagram
-
-
-
?
myo-inositol + O2
d-glucuronate
show the reaction diagram
myo-inositol + O2
D-glucuronate + H2O
show the reaction diagram
myo-inositol + O2
D-glucuronic acid + H2O
show the reaction diagram
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
myo-inositol + O2
d-glucuronate
show the reaction diagram
myo-inositol + O2
D-glucuronic acid + H2O
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
flavin
-
5. 6 mMol per mol of enzyme
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2,4,6-Tripyridyl-(2)-1,3,5-triazine
-
-
2-Thenoyltrifluoroacetone
-
slight
3-Aminopicolinate
-
-
5,5'-dithiobis(2-nitrobenzoate)
-
-
6-(4-hydroxy-3,5-dimethoxyphenyl)-4,8-dihydronaphthalene-1,3,8-triol
-
docking energy level (Kcal/mol): -6.9602
8-hydroxyquinoline
alpha,alpha'-bipyridine
-
-
alpha-ketoglutarate
-
-
arsenite
-
-
ascochitine
-
docking energy level (Kcal/mol): -9.5382
Barbital
-
-
cyanide
D-Glucodialdehyde
-
weak
diethyldithiocarbamate
-
-
EDTA
-
-
Epi-Inositol
-
-
Fe3+
-
-
ferricyanide
-
-
ferrocyanide
-
-
Furoylthiofluoroacetone
-
slight
-
glyoxylate
-
-
H2O2
-
-
heritonin
-
docking energy level (Kcal/mol): -10.4072
hydroxylamine
-
-
iodoacetate
menadione
-
-
myo-Inosose-1
-
-
N-ethylmaleimide
-
slight
o-phenanthroline
oxalacetate
-
-
oxalate
-
-
p-chloromercuribenzoate
Phenobarbital
-
-
Phenylmercuric nitrate
-
-
pyruvate
-
-
Quinacrine hydrochloride
-
slight
riboflavin phosphate
-
-
Sodium borohydride
-
-
stigmasterol
-
docking energy level (Kcal/mol): -14.589
taraxasterol
-
docking energy level (Kcal/mol): -14.8894
tetrahydrofolic acid
-
-
tretinoin
-
docking energy level (Kcal/mol): -12.1034
UDP
-
-
Uridine diphosphoglucose
-
-
xanthurenic acid
-
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3-Mercaptopicolinate
-
activation
cysteine
D-Cysteine
-
best activation system: 1 mM Fe(II) and 2 mM cysteine, L-cysteine can be replaced by D-cysteine, DL-penicillamine or gamma-L-glutamyl-L-cysteine
DL-Penicillamine
-
best activation system: 1 mM Fe(II) and 2 mM cysteine, L-cysteine can be replaced by D-cysteine, DL-penicillamine or gamma-L-glutamyl-L-cysteine
gamma-L-glutamyl-L-cysteine
-
best activation system: 1 mM Fe(II) and 2 mM cysteine, L-cysteine can be replaced by D-cysteine, DL-penicillamine or gamma-L-glutamyl-L-cysteine
L-cysteine
quinolinate
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.2 - 22.1
Inositol
3.3 - 45
myo-inositol
0.0095 - 0.06
O2
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
7.22
Inositol
Rattus norvegicus
-
-
0.183
myo-inositol
Sus scrofa
Q8WN98
with Fe(2+) and L-cysteine as activators
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.02
1,10-phenanthroline
-
0.01
p-chloromercuribenzoate
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.005
-
culture condition: 1 day, 30C
0.008
-
culture condition: 2 day, 30C
0.01
-
culture condition: 3 day, 30C
0.015
-
culture condition: 12 h, without supplementation of myo-inositol
0.028
-
culture condition: without supplementation of myo-inositol
0.042
-
culture condition: 12 h, supplementation with 60 mM myo-inositol, 1 mM Fe(NH4)2(SO4)2, 2 mM L-cysteine
0.076
-
culture condition: 12 h, supplementation with 60 mM myo-inositol
0.18
-
culture condition: 6 h, supplementation with 60 mM myo-inositol, 1 mM Fe(NH4)2(SO4)2, 2 mM L-cysteine
0.43
-
culture condition: 6 h, supplementation with 60 mM myo-inositol
additional information
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.8 - 7.2
-
-
8
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.5 - 10
almost no activity at pH 4.5, approx. 10% of maximal ativity at pH 10.0, approx. 70% of maximal activity at pH 8.0, i.e. a second optima
6.5 - 7.4
-
sharp decrease of activity below pH 6.5 and above pH 7.4
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
35
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0 - 60
approx. 30% of maximal activity at 0C and 50C, respectively
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
is expressed at low levels in cell types where diabetic complications occur
Manually annotated by BRENDA team
-
MIOX1 and MIOX2 are expressed in almost all tissues of the plant
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
32000
-
SDS-PAGE
32663
electrospray MS determination, gel filtration, SDS-PAGE, sedimentation equilibirum, enzyme does not undergo oligomerization in the presence of myo-inositol
65000
-
pig, gel filtration, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
-
2 * 16800, dimer is the elementary active enzyme-building unit, oligomer (MW 270000) can be dissociated under mild conditions to monomers (MW 16800)
dodecamer
-
12 * 17000, smallest active unit is tetramer, it is in a pH-dependent equilibrium with species consisting of 8, 12 and 16 subunits
hexadecamer
-
16 * 17000, smallest active unit is tetramer, it is in a pH-dependent equilibrium with species consisting of 8, 12 and 16 subunits
monomer
octamer
-
8 * 17000, smallest active unit is tetramer, it is in a pH-dependent equilibrium with species consisting of 8, 12 and 16 subunits
oligomer
-
x * 16800, smallest active unit is tetramer, it is in a pH-dependent equilibrium with species consisting of 8, 12 and 16 subunits
tetramer
-
4 * 17000, gel filtration, smallest active unit is tetramer, which is in a pH-dependent equilibrium with species consisting of 8, 12 and 16 subunits
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
-
mutants with substituted phosphorylation sites have a minimal increase in activity. Treatment of cells with PKC, PKA, and PDK1 kinase activators increased activity, whereas inhibitors reduced it. Protein kinases A, C, and PDK1 are capable of phosphorylating mouse in both prokaryotic and eukaryotic systems. Using deletion constructs it is shown that the N-terminus contains the critical phosphorylation sites that are highly relevant to the functionality of the protein
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
in complex with myo-inosose-1 bound in a terminal mode to the enzyme's diiron cluster site. The N-terminus is important, through coordination of a set of loops covering the active site, in shielding the active site during catalysis. Role of residue K127 in governing the access o the diiron cluster
-
crystals grow from a solution containing 20 mg/ml MIOX, 20 mM myo-inositol, 50 mM Mes pH 6.0, 50 mM NaCl, 2 mM Tris(2-carboxyethyl)-phosphine hydrochloride and 4.4 M sodium formate
-
sitting drop vapour diffusion method producing crystals from unbuffered 4.4 M sodium formate
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
34
-
inactivation during 15 min assay
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
after storage at 4C for few weeks, a specific truncation due to degradation is observed, extended storage also causes the accumulation of a small proportion of apparantly dimerized MIOX
Catalase protects from H2O2 inactivation
-
Completely active even in absence of Fe(II) and cysteine if it has been stored at -20C for days to weeks at pH 6.0 with 1 mM glutathione
-
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
Highly unstable in presence of oxygen, in early stages of inactivation: reactivation by reducing agents like NaBH4
-
6870
Sensitive to oxidants: H2O2, ferricyanide, FeCl3, CuSO4, HgCl2
-
6875
Sensitive to reductants, e.g. ferrocyanide
-
6875
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C for weeks or months: activation -20C, completely active even in absence of Fe(II) and cysteine for days to weeks at pH 6.0 with 1 mM glutathione
-
-20C, extensive loss of activity after 1 or 2 days
-
0C, 12 h, extensive loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
affinity chromatography
-
AG1-X8 resin column chromatography
-
ammonium sulfate, DEAE-column, butyl-Sepharose, Superdex 75, Mono Q
DEAESepharose FF column chromatography and Sephacryl S-200 HR chromatography
-
Ni2+-affinity chromatography
-
Ni2+-affinity chromatography and S200 HR10/30 column chromatography
-
recombinant MIOX
recombinant MIOX4
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Escherichia coli in the presence of the iron chelator, 1,10-phenanthroline to create iron-free MIOX
-
expression in Agrobacterium tumefaciens; expression in Agrobacterium tumefaciens; expression in Agrobacterium tumefaciens; expression in Agrobacterium tumefaciens
expression in epithelial cell line LLC-PK1
-
expression in Escherichia coli
genotyping of MIOX in Caucasian type I diabetes mellitus patients, overview
-
open reading frame of 849 base pairs
transfection into NRK-52E cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
445.7fold gene induction in syncytia induced by nematode Heterodera schachtii; 445.7fold gene induction in syncytia induced by nematode Heterodera schachtii; 7.64fold gene induction in syncytia induced by nematode Heterodera schachtii; gene induction in syncytia induced by nematode Heterodera schachtii
antioxidants N-acetylcysteine, beta-naphthoflavone, and tertiary butyl hydroquinone reduces MIOX expression
-
diabetic, nephropathy
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genes encoding the enzyme are strongly expressed in syncytia induced by the beet cyst nematode Heterodera schachtii in Arabidopsis roots
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high glucose levels, exposure of cells to oxidants H2O2 and methylglyoxal up-regulates MIOX expression
-
MIOX2 expression is suppressed by exogenous glucose addition in the shoot, but not in the root; MIOX4 expression is suppressed by exogenous glucose addition in the shoot,but not in the root
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
DELTA miox 1+2
double mutant, smaller syncytia, less female nematodes per plant; double mutant, smaller syncytia, less female nematodes per plant
delta miox 4+5
double mutant, smaller syncytia, less female nematodes per plant; double mutant, smaller syncytia, less female nematodes per plant
DELTA miox1
single knockout mutant of one allele of MIOX
delta miox2
single knockout mutant of one allele of MIOX
delta miox5
single knockout mutant of one allele of MIOX; single knockout mutant of one allele of MIOX
S24A/S205A/S218A/T29A/T69A
-
mutated putative PKA phosphorylation sites: mutant is also phosphorylated but to a minor degree
S24A/S205A/S218A/T29A/T69A/S64A/T40A/T49A/T69A/T253A
-
mutated putative PKA and PKC phosphorylation sites: mutant is also phosphorylated but to a minor degree
S64A/T40A/T49A/T69A/T253A
-
mutated putative PKC phosphorylation sites: mutant is also phosphorylated but to a minor degree