Information on EC 1.14.13.9 - kynurenine 3-monooxygenase

Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


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

EC NUMBER
COMMENTARY
1.14.13.9
-
RECOMMENDED NAME
GeneOntology No.
kynurenine 3-monooxygenase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
L-kynurenine + NADPH + H+ + O2 = 3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Metabolic pathways
-
tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde
-
tryptophan degradation XI (mammalian, via kynurenine)
-
Tryptophan metabolism
-
SYSTEMATIC NAME
IUBMB Comments
L-kynurenine,NADPH:oxygen oxidoreductase (3-hydroxylating)
A flavoprotein (FAD).
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
cinnabar
A1Z745
-
cinnabar
Q95NP6
-
EC 1.14.1.2
-
-
formerly
-
EC 1.99.1.5
-
-
formerly
-
KMO
Q86PM2
-
KMO
Aedes aegypti Liverpool
Q86PM2
-
-
KMO
Bombyx mori C108
-
-
-
KMO
Pseudomonas fluorescens 17400
-
-
-
KMO
Q9MZS9
-
KYN-OHase
-
-
kynurenine 3-hydroxylase
-
-
-
-
kynurenine 3-hydroxylase
Q8ISJ5
-
kynurenine 3-hydroxylase
-
-
kynurenine 3-hydroxylase
-
-
kynurenine hydroxylase
-
-
-
-
kynurenine hydroxylase
Q86PM2
-
kynurenine hydroxylase
Aedes aegypti Liverpool
Q86PM2
-
-
kynurenine hydroxylase
-
-
kynurenine monooxygenase
Q86PM2
-
kynurenine monooxygenase
Aedes aegypti Liverpool
Q86PM2
-
-
L-kynurenine 3-monooxygenase
Q9MZS9
-
L-kynurenine,NADPH2:oxygen oxidoreductase (3-hydroxylating)
-
-
oxygenase, kynurenine 3-mono-
-
-
-
-
L-kynurenine-3-hydroxylase
-
-
-
-
additional information
Q86PM2
the enzyme is a member of the glutathione reductase structural family
additional information
Aedes aegypti Liverpool
Q86PM2
the enzyme is a member of the glutathione reductase structural family
-
CAS REGISTRY NUMBER
COMMENTARY
9029-61-2
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
yellow fever mosquito, black-eyed Liverpool strain
SwissProt
Manually annotated by BRENDA team
Aedes aegypti Liverpool
yellow fever mosquito, black-eyed Liverpool strain
SwissProt
Manually annotated by BRENDA team
strain C108
-
-
Manually annotated by BRENDA team
Bombyx mori C108
strain C108
-
-
Manually annotated by BRENDA team
gene Tccn
SwissProt
Manually annotated by BRENDA team
wild-type and 3 mutants
-
-
Manually annotated by BRENDA team
ovariectomized female cynomolgus monkeys
-
-
Manually annotated by BRENDA team
male rhesus macaques
-
-
Manually annotated by BRENDA team
female mongolian gerbil
-
-
Manually annotated by BRENDA team
mouse, strain D57Bl/6J
-
-
Manually annotated by BRENDA team
male, 4-month-old diabetic/hyperlipidemic New Zealand White rabbits
-
-
Manually annotated by BRENDA team
strain 17400
-
-
Manually annotated by BRENDA team
Pseudomonas fluorescens 17400
strain 17400
-
-
Manually annotated by BRENDA team
female wistar rat
-
-
Manually annotated by BRENDA team
male SpragueDawley rats
-
-
Manually annotated by BRENDA team
male wistar rat
-
-
Manually annotated by BRENDA team
Osborne-Mendel strain
-
-
Manually annotated by BRENDA team
SpragueDawley rats of ages 1 week, 23, 12 and 18 months
-
-
Manually annotated by BRENDA team
Rattus norvegicus Osborne-Mendel
Osborne-Mendel strain
-
-
Manually annotated by BRENDA team
diverse strains
-
-
Manually annotated by BRENDA team
mutant E105 has an enzymatic defect of kynurenine 3-hydroxylase
-
-
Manually annotated by BRENDA team
wild type and different sterol mutants
-
-
Manually annotated by BRENDA team
pig
-
-
Manually annotated by BRENDA team
red flour beetle
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
physiological function
-
T helper 17 cells preferentially express kynurenine 3-monooxygenase. Enzyme inhibition, either with a specific inhibitor or via siRNA-mediated silencing, markedly increases IL-17 productionin vitro, whereas IFN-gamma production by T helper 1 cells is unaffected. Inhibition of kynurenine 3-monooxygenase significantly exacerbates disease in a Th17-driven model of autoimmune gastritis
additional information
Q9MZS9
the C-terminal region of pig liver KMO plays a dual role. First, it is required for the enzymatic activity. Second, it functions as a mitochondrial targeting signal
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
show the reaction diagram
-
enzyme inhibition in immature rats shifts cerebral kynurenine pathway metabolism toward increased kynurenic acid formation, overview
-
-
?
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
show the reaction diagram
-
the enzyme is involved in the kynurenine pathway of tryptophan metabolsim, overview
-
-
?
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
show the reaction diagram
-
the reaction is central to the tryptophan degradative pathway, overview, and takes place within microglial cells defining cellular concentrations of the N-methyl-D-aspatate receptor agonist quinolinate and antagonist kynurenate
the product acts as apoptotic signal
-
ir
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
show the reaction diagram
-
enzyme activity depends on the reduction state of the enzyme
-
-
ir
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
show the reaction diagram
Pseudomonas fluorescens 17400
-
the reaction is central to the tryptophan degradative pathway, overview, and takes place within microglial cells defining cellular concentrations of the N-methyl-D-aspatate receptor agonist quinolinate and antagonist kynurenate
the product acts as apoptotic signal
-
ir
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
show the reaction diagram
Pseudomonas fluorescens 17400
-
enzyme activity depends on the reduction state of the enzyme
-
-
ir
L-kynurenine + NADH + H+ + O2
3-hydroxy-L-kynurenine + NAD+ + H2O
show the reaction diagram
-, Q86PM2
-
-
-
-
L-kynurenine + NADH + H+ + O2
3-hydroxy-L-kynurenine + NAD+ + H2O
show the reaction diagram
Q9MZS9, -
-
-
-
?
L-kynurenine + NADH + H+ + O2
3-hydroxy-L-kynurenine + NAD+ + H2O
show the reaction diagram
Aedes aegypti Liverpool
Q86PM2
-
-
-
-
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
Q9MZS9, -
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in Parkinsonian monkeys, enzyme regulation and involvement in Parkinson's disease, overview
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
-
-
r
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-, Q8ISJ5
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-, Q86PM2
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
NADH is less effective
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
no reaction with D-isomer
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-, Q86PM2
enzyme has a key role in L-tryptophan catabolism and in synthesis of ommochrome pigments in the eyes of the mosquitos
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
enzyme is involved in L-tryptophan catabolism, pathway regulation in comparison to other species, overview
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
function of the enzyme may change from a role in immunosuppression at the maternal-fetal interface in early pregnancy to one associated with regulation of fetoplacental blood flow or placental metabolism in late gestation
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
step in L-tryptophan catabolism, overview
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-, Q8ISJ5
the enzyme is not involved in regulation of 3-hydroxy-L-kynurenine level in vivo
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
binding of L-kynurenine to the oxidized enzyme is relatively slow and involves at least two reversible steps
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
Aedes aegypti Liverpool
Q86PM2
-, enzyme has a key role in L-tryptophan catabolism and in synthesis of ommochrome pigments in the eyes of the mosquitos
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
Rattus norvegicus Osborne-Mendel
-
no reaction with D-isomer
-
?
L-kynurenine + NADPH + O2
? + NAD+
show the reaction diagram
-
-
-
-
?
L-kynurenine + NADPH + O2
? + NAD+
show the reaction diagram
-
increased activity in the spinal cord with experimental allergic encephalopathy
-
-
?
L-kynurenine + NADPH + O2
? + NAD+
show the reaction diagram
-
rate limiting step in the pyridine nucleotide biosynthesis from tryptophan
-
-
?
L-kynurenine + NADPH + O2
? + NAD+
show the reaction diagram
-
increased activity in injured brain regions following cerebral ischemia
-
-
?
L-kynurenine + NADPH + O2
? + NAD+
show the reaction diagram
-
key enzyme in the kynurenine pathway of tryptophan degradation
-
-
?
o-hydroxybenzoyl-DL-alanine + NADPH + O2
? + NAD+
show the reaction diagram
Rattus norvegicus, Rattus norvegicus Osborne-Mendel
-
about 25% of the activity with L-kynurenine
-
-
?
L-kynurenine + NADPH + O2
? + NAD+
show the reaction diagram
Rattus norvegicus Osborne-Mendel
-
-
-
-
?
additional information
?
-
-
catalyzes NADH- and NADPH-linked reductions of low molecular weight acceptors such as 2,6-dichlorophenolindophenol and ferricyanide
-
-
-
additional information
?
-
A1Z745
enzyme is involved in eye pigmentation
-
-
-
additional information
?
-
-
the enzyme is a very potent suppressor of toxicity of a fragment of the protein huntingtin, Htt, which causes the neurodegenerative Huntington disease by aggregation in nuclear and cytoplasmic inclusion bodies
-
-
-
additional information
?
-
-
the enzyme is a very potent suppressor of toxicity of a fragment of the protein huntingtin, Htt, which causes the neurodegenerative Huntington disease in humans by aggregation in nuclear and cytoplasmic inclusion bodies
-
-
-
additional information
?
-
-
age affects the enzyme activities of tryptophan metabolism along the kynurenine pathway, one of the various tryptophan metabolic routes, kynurenine 3-monooxygenase activity progressively decreases with age in liver and kidney of newborn to mature rats, quantitative overview
-
-
-
additional information
?
-
-
the kynurenine pathway of tryptophan degradation contains three neuroactive metabolites: the neuroinhibitory agent kynurenic acid and, in a competing branch, the free radical generator 3-hydroxykynurenine and the excitotoxin quinolinic acid, newborn mice delivered by UPF 648-treated mothers and immediately exposed to neonatal asphyxia show further enhanced brain kynurenic acid levels, overview
-
-
-
additional information
?
-
-
the kynurenine pathway of tryptophan degradation contains three neuroactive metabolites: the neuroinhibitory agent kynurenic acid and, in a competing branch, the free radical generator 3-hydroxykynurenine and the excitotoxin quinolinic acid, rat pups delivered by UPF 648-treated mothers and immediately exposed to neonatal asphyxia show further enhanced brain kynurenic acid levels, overview
-
-
-
additional information
?
-
-
the enzyme is responsible for driving formation of neurotoxic and neuroprotective kynurenine metabolites, regulation mechanism, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
show the reaction diagram
-
enzyme inhibition in immature rats shifts cerebral kynurenine pathway metabolism toward increased kynurenic acid formation, overview
-
-
?
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
show the reaction diagram
-
the enzyme is involved in the kynurenine pathway of tryptophan metabolsim, overview
-
-
?
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
show the reaction diagram
Pseudomonas fluorescens, Pseudomonas fluorescens 17400
-
the reaction is central to the tryptophan degradative pathway, overview, and takes place within microglial cells defining cellular concentrations of the N-methyl-D-aspatate receptor agonist quinolinate and antagonist kynurenate
the product acts as apoptotic signal
-
ir
L-kynurenine + NADH + H+ + O2
3-hydroxy-L-kynurenine + NAD+ + H2O
show the reaction diagram
Q9MZS9, -
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
Q9MZS9, -
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in Parkinsonian monkeys, enzyme regulation and involvement in Parkinson's disease, overview
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-, Q86PM2
enzyme has a key role in L-tryptophan catabolism and in synthesis of ommochrome pigments in the eyes of the mosquitos
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
enzyme is involved in L-tryptophan catabolism, pathway regulation in comparison to other species, overview
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
function of the enzyme may change from a role in immunosuppression at the maternal-fetal interface in early pregnancy to one associated with regulation of fetoplacental blood flow or placental metabolism in late gestation
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-
step in L-tryptophan catabolism, overview
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
-, Q8ISJ5
the enzyme is not involved in regulation of 3-hydroxy-L-kynurenine level in vivo
-
-
?
L-kynurenine + NADPH + O2
? + NAD+
show the reaction diagram
-
-
-
-
?
L-kynurenine + NADPH + O2
? + NAD+
show the reaction diagram
-
increased activity in the spinal cord with experimental allergic encephalopathy
-
-
?
L-kynurenine + NADPH + O2
? + NAD+
show the reaction diagram
-
rate limiting step in the pyridine nucleotide biosynthesis from tryptophan
-
-
?
L-kynurenine + NADPH + O2
? + NAD+
show the reaction diagram
-
increased activity in injured brain regions following cerebral ischemia
-
-
?
L-kynurenine + NADPH + O2
? + NAD+
show the reaction diagram
-
key enzyme in the kynurenine pathway of tryptophan degradation
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
show the reaction diagram
Aedes aegypti Liverpool
Q86PM2
enzyme has a key role in L-tryptophan catabolism and in synthesis of ommochrome pigments in the eyes of the mosquitos
-
-
?
L-kynurenine + NADPH + O2
? + NAD+
show the reaction diagram
Rattus norvegicus Osborne-Mendel
-
-
-
-
?
additional information
?
-
A1Z745
enzyme is involved in eye pigmentation
-
-
-
additional information
?
-
-
the enzyme is a very potent suppressor of toxicity of a fragment of the protein huntingtin, Htt, which causes the neurodegenerative Huntington disease by aggregation in nuclear and cytoplasmic inclusion bodies
-
-
-
additional information
?
-
-
the enzyme is a very potent suppressor of toxicity of a fragment of the protein huntingtin, Htt, which causes the neurodegenerative Huntington disease in humans by aggregation in nuclear and cytoplasmic inclusion bodies
-
-
-
additional information
?
-
-
age affects the enzyme activities of tryptophan metabolism along the kynurenine pathway, one of the various tryptophan metabolic routes, kynurenine 3-monooxygenase activity progressively decreases with age in liver and kidney of newborn to mature rats, quantitative overview
-
-
-
additional information
?
-
-
the kynurenine pathway of tryptophan degradation contains three neuroactive metabolites: the neuroinhibitory agent kynurenic acid and, in a competing branch, the free radical generator 3-hydroxykynurenine and the excitotoxin quinolinic acid, newborn mice delivered by UPF 648-treated mothers and immediately exposed to neonatal asphyxia show further enhanced brain kynurenic acid levels, overview
-
-
-
additional information
?
-
-
the kynurenine pathway of tryptophan degradation contains three neuroactive metabolites: the neuroinhibitory agent kynurenic acid and, in a competing branch, the free radical generator 3-hydroxykynurenine and the excitotoxin quinolinic acid, rat pups delivered by UPF 648-treated mothers and immediately exposed to neonatal asphyxia show further enhanced brain kynurenic acid levels, overview
-
-
-
additional information
?
-
-
the enzyme is responsible for driving formation of neurotoxic and neuroprotective kynurenine metabolites, regulation mechanism, overview
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
FAD
-
4 mol of FAD per subunit; flavoprotein
FAD
-
one molecule non-covalently bound FAD per molecule of enzyme
FAD
-, Q8ISJ5
binding domain at the N-terminus comprising residues 23-166
FAD
Q86PM2
consensus domain sequence, probably FAD-containing
FAD
Q9MZS9
-
NADH
-
less effective than NADPH
NADH
-
less effective than NADPH
NADH
Q86PM2
low activity, ineffective cofactor
NADH
Q9MZS9
-
NADPH
-, Q8ISJ5
dependent on, the Gly-X-Gly-X-X-Gly motif, residues 27-32, and the hydrophobic amino acid residues at positions 23, 25, 36, 39, 46, and 48 are indispensable for correct folding of the beta1-alpha-beta2-structure of the dinucleotide binding domain
NADPH
Q86PM2
highly preferred cofactor with respect to NADH
NADPH
-
dependent on
NADPH
Q9MZS9
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Br-
-
strong stimulation
Cl-
-
strong stimulation at 0.02 M
CN-
-
stimulates
F-
-
stimulates
I-
-
stimulates
NaCl
-
stabilizes
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(1S,2S)-2-(3,4-dichlorobenzoyl)-cyclopropane-1-carboxylic acid
-
KMO inhibitor UPF 648, totally blocks KMO at 0.1 and 0.01 mM and is still highly active at 0.001 mM (81% inhibition). It reduces 3-hydroxykynurenine synthesis by 64% without affecting kynurenic acid formation. In neuron-depleted striata, UPF 648 decreases both 3-hydroxykynurenine and quinolinic acid production by 77% and 66%, respectively and also raises kynurenic acid synthesis by 27%. 0.1 mM UPF 648 blocks KMO in both lesioned and contralateral striatum, but does not interfere with KAT activity in either tissue
(m-nitrobenzoyl)-alanine
-
mNBA, leads to an increase of L-kynurenine and kynurenic acid concentrations in the brain cortex after application in vivo
(m-nitrobenzoyl)-alanine
-
various pyrrolo[3,2-c]quinoline derivates cause enzyme inhibition
(m-nitrobenzoyl)-alanine
-
50% inhibition at 0.9 micromolar
(R,S)-2-amino-oxo-4-(3',4'-dichlorophenyl)butanoic acid
-
FCE 28833, 50% inhibition at 0.2 microM, blocks not only the cerebral but also the peripheral enzyme
(R,S)-2-amino-oxo-4-(3'-4'-dichlorophenyl)butanoic acid
-
-
(S)-9-(4-aminopiperazine-1-yl)-8-fluoro-3-methyl-6-oxo-2,3,5,6-tetrahydro-4H-1-oxa-3a-azaphenalene-5-carboxylic acid
-
does not affect KMO activity significantly, 1 mM inhibits by 17%
2-benzyl-4-(3,4-dichlorophenyl)-4-oxo-butanoic acid
-
-
2-hydroxy-4-(3,4-dichlorophenyl)-4-oxobutanoic acid
-
-
2-oxo acid derivatives
-
of the 3 branched chain amino acids
2-oxoglutarate
-
mixed type inhibitor
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
-
Ro-61-8048, 50% inhibition at 37 nM
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
-
leads to an increase of L-kynurenine and kynurenic acid concentrations in the brain cortex after application in vivo
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
-
inhibition after oral or intraperitoneal administration
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
-
i.e. Ro 61-8048, high-affinity low molecular inhibitor
3-nitrobenzoylalanine
-
-
4-amino-N-[4-[2-fluoro-5-(trifluoromethyl)phenyl]thiazol-2-yl]benzenesulfonamide
-
50% inhibition at 19nM
7-chloro-3-methyl-1H-pyrrolo[3,2-c]quinoline-4-carboxylic acid
-
relatively potent and selective inhibitor
alpha-Ketoisocaproate
-
non competitive inhibition
anthranilic acid
-
22% inhibition at 2 mM and 11% inhibition at 0.2 mM
benzoylalanine
-
KMO inhibitor that mimics the substrate structure, and also stimulates reduction of the flavin by NADPH
chloride
Q86PM2
mixed-type inhibition
Cl-
-
70% inhibition with 0.1 M NaCl or KCl, competitive with respect to NADPH and non-competitive with respect to L-kynurenine
CN-
-
inhibition at 0.01 M
CN-
-
high concentration
deamino-(R,S)-3,4-dichlorobenzoylalanine
-
desamino FCE 28833
-
EDTA
-
68% inhibition at 2 mM
KCl
-
high concentration
Kynurenic acid
-
13% inhibition at 2 mM and 5% inhibition at 0.2 mM
L-tryptophan
-
35% inhibition at 2 mM and 22% inhibition at 0.2 mM
p-chloromercuribenzoate
-
weak, 50% inhibition at 0.4 M
pyridoxal
-
less potent than pyridoxal phosphate
pyridoxal 5'-phosphate
-
non competitive inhibition
pyridoxal 5'-phosphate
Q86PM2
noncompetitive
pyruvate
-
mixed type inhibitor
Ro 61-8048
-
high-affinity low molecular inhibitor
Ro 61-8048
-
-
UPF 648
-
in vivo inhibition
UPF 648
P38169
UPF 648 binds close to the FAD cofactor and perturbs the local active site structure, preventing productive binding of the substrate kynurenine
xanthurenic acid
-
48% inhibition at 2 mM and 13% inhibition at 0.2 mM
m-nitrobenzoylalanine
-
KMO inhibitor that mimics the substrate structure, and also stimulates reduction of the flavin by NADPH
additional information
-
inhibition by N-(4-phenylthiazol-2-yl)benzenesulfonamides with various modifications
-
additional information
-
inhibition by various 2-amino-4-aryl-4-oxobut-2-enoic acids and esters at 10 micromolar; inhibition by various 4-aryl-2-hyroxy-4-oxobut-2-enoic acids and esters at 10 micromolar
-
additional information
-
the specific enzyme activity is not affected by cloricromene in vitro and in vivo in liver and kidney
-
additional information
-
targeted inhibition of KMO is a viable strategy for achieving local elevation of kynurenate concentrations
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
Thiocyanate
-
0.01 M
additional information
-
a systemic inflammatory challenge stimulates KMO expression in brain, increased enzyme expression is observed in rat brain 24 h post lipopolysaccharide treatment, without any change in kynurenine aminotransferase II expression
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00012
-
FAD
-
-
0.0003
-
FAD
-
-
0.012
-
kynurenine
-
recombinant enzyme, pH 7.5, 5C
0.014
-
kynurenine
-
liver lysate, pH 7.4, 25C
0.025
-
kynurenine
-
-
0.053
-
kynurenine
-
recombinant enzyme, pH 7.5, 25C
0.33
-
kynurenine
-
-
0.0164
-
L-kynurenine
-
-
0.04
-
L-kynurenine
-
under aerobic conditions
0.045
-
L-kynurenine
-
under unaerobic conditions
5.17
-
NADH
Q86PM2
recombinant enzyme, pH 7.5, 37C
0.0085
-
NADPH
-
recombinant enzyme, pH 7.5, 5C
0.016
-
NADPH
-
under aerobic conditions
0.017
-
NADPH
-
under unaerobic conditions
0.023
-
NADPH
-
-
0.091
-
NADPH
-
recombinant enzyme, pH 7.5, 25C
0.82
-
NADPH
Q86PM2
recombinant enzyme, pH 7.5, 37C
0.034
-
O2
-
recombinant enzyme, pH 7.5, 5C
0.071
-
O2
-
recombinant enzyme, pH 7.5, 25C
0.89
-
L-kynurenine
Q86PM2
recombinant enzyme, pH 7.5, 37C
additional information
-
additional information
Q86PM2
kinetics
-
additional information
-
additional information
-
steady-state kinetics and ligand perturbation of flavin fluorescence, overview
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1.3
-
kynurenine
-
recombinant enzyme, pH 7.5, 5C
4.9
-
kynurenine
-
recombinant enzyme, pH 7.5, 25C
1.88
-
L-kynurenine
Q86PM2
recombinant enzyme, pH 7.5, 37C
0.85
-
NADH
Q86PM2
recombinant enzyme, pH 7.5, 37C
2.03
-
NADPH
Q86PM2
recombinant enzyme, pH 7.5, 37C
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
9.5e-05
-
(R,S)-2-amino-oxo-4-(3'-4'-dichlorophenyl)butanoic acid
-
competitive inhibitor
4.8e-06
-
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
-
competitive inhibitor
4.2
-
alpha-Ketoisocaproate
-
inhibition for L-kynurenine
8.3
-
alpha-Ketoisocaproate
-
inhibition for NADPH
11.2
-
chloride
Q86PM2
recombinant enzyme, with respect to L-kynurenine, pH 7.5, 37C
24.5
-
chloride
Q86PM2
recombinant enzyme, with respect to NADPH, pH 7.5, 37C
1
-
pyridoxal
-
-
0.17
-
pyridoxal 5'-phosphate
Q86PM2
recombinant enzyme, with respect to NADPH, pH 7.5, 37C
0.19
-
pyridoxal 5'-phosphate
-
-
0.27
-
pyridoxal 5'-phosphate
Q86PM2
recombinant enzyme, with respect to L-kynurenine, pH 7.5, 37C
IC50 VALUE [mM]
IC50 VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2.5e-05
-
deamino-(R,S)-3,4-dichlorobenzoylalanine
-
pH 7.4, 25C
-
3.5e-05
-
Ro 61-8048
-
pH 7.4, 25C
3e-07
-
UPF 648
-
pH 7.4, 25C
7.4e-05
-
UPF 648
P38169
pH 8.0, 30C
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
1.2e-05
-
-
liver of 2-3 months-old rats
0.0004
-
-
activity in kidney
0.0005
-
-
kidney
0.001
-
-
liver
0.001
-
-
activity in liver
0.0015
-
-
activity in liver and in kidney
0.0022
-
-
liver
0.0025
-
-
liver
0.0025
-
-
kidney
0.004
-
-
kidney
0.028
-
-
NADPH oxidase activity
0.095
-
-, Q8ISJ5
recombinant enzyme in crude Sf9 cell lysate
0.866
-
-, Q8ISJ5
purified recombinant enzyme
2
-
-
fusion protein with glutathione-S-transferase
3.15
-
-
purified recombinant enzyme
47
-
-
native
additional information
-
-
20000000 cpm per micromole
additional information
-
-
specific activities of apoenzyme and holoenzyme with different electron acceptors
additional information
-
-
enzyme activity at different temperatures in different strains
additional information
-
-
enzyme activity with different cofactors and under anaerobic conditions
additional information
-
-
-
additional information
-
-
specific activity in various organs
additional information
-
-
-
additional information
-
-
specific activity in organs of rats with experimental allergic encephalopathy
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
-
-, Q8ISJ5
-
7.5
-
-
fusion protein with glutathione-S-transferase
7.5
-
Q86PM2
-
8
-
Q9MZS9
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
9
-
about 50% of maximal activity at pH 7 and 9
7
9.3
-
about 50% of maximal activity at pH 7 and 9.3
7.1
8.9
-
about 50% of maximal activity at pH 7.1 and 8.9
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
23
-
-
assay at
25
-
-
assay at
30
-
-
assay at
37
-
Q9MZS9
assay at
40
-
Q86PM2
-
TEMPERATURE RANGE
TEMPERATURE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7
10
-
50% activity at 7C and 10C
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
villous, endothel
Manually annotated by BRENDA team
-
neurons and astrocytes
Manually annotated by BRENDA team
-
lesioned and contralateral striatum
Manually annotated by BRENDA team
-
vascular, of villous blood vessels
Manually annotated by BRENDA team
-
enzyme expression
Manually annotated by BRENDA team
Bombyx mori C108
-
enzyme expression
-
Manually annotated by BRENDA team
-
enzyme activity decreases significantly with age
Manually annotated by BRENDA team
-
enzyme activity decreases significantly with age
Manually annotated by BRENDA team
Rattus norvegicus Osborne-Mendel
-
-
-
Manually annotated by BRENDA team
-
in first and second trimester of the placenta, within the fetal villus
Manually annotated by BRENDA team
-
enzyme expression
Manually annotated by BRENDA team
Bombyx mori C108
-
enzyme expression
-
Manually annotated by BRENDA team
Pseudomonas fluorescens 17400
-
-
-
Manually annotated by BRENDA team
-
enzyme expression
Manually annotated by BRENDA team
Bombyx mori C108
-
enzyme expression
-
Manually annotated by BRENDA team
-
especially in stromal and glandular epithelium in the first trimester decidua
Manually annotated by BRENDA team
-
in first and second trimester of the placenta
Manually annotated by BRENDA team
-
in first and second trimester of the placenta
Manually annotated by BRENDA team
-
T helper 17 cells preferentially express kynurenine 3-monooxygenase. Enzyme inhibition, either with a specific inhibitor or via siRNA-mediated silencing, markedly increases IL-17 productionin vitro, whereas IFN-gamma production by T helper 1 cells is unaffected. Inhibition of kynurenine 3-monooxygenase significantly exacerbates disease in a Th17-driven model of autoimmune gastritis
Manually annotated by BRENDA team
additional information
-, Q8ISJ5
constitutive expression of the enzyme in all developmental stages from egg via larva and pupa to adult mosquito
Manually annotated by BRENDA team
additional information
-
localization in placenta, overview
Manually annotated by BRENDA team
additional information
-
MPTP-treated monkeys
Manually annotated by BRENDA team
additional information
-
enzyme expression analysis in untreated and in brain after induction of inflammation, overview
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
49000
-
-
SDS-PAGE
55000
-
-
SDS-PAGE
55760
-
-
calculated from primary sequence
55760
-
-
calculated from primary sequence
200000
-
-
or more, gel filtration, SDS-PAGE
345000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-, Q8ISJ5
x * 60000, recombinant enzyme, SDS-PAGE
?
Q86PM2
x * 54000, recombinant soluble enzyme not counting the His-tag, SDS-PAGE
?
-
x * 50000, recombinant enzyme, SDS-PAGE
?
Aedes aegypti Liverpool
-
x * 54000, recombinant soluble enzyme not counting the His-tag, SDS-PAGE
-
?
Pseudomonas fluorescens 17400
-
x * 50000, recombinant enzyme, SDS-PAGE
-
dimer
-
2 * 160000 in 0.2% Triton-X100, SDS-PAGE
additional information
-, Q8ISJ5
structural analysis
additional information
Q9MZS9
the C-terminal region is required for the enzymatic activity and functions as a mitochondrial targeting signal
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
crystal structure, in the free form and in complex with the tight-binding inhibitor UPF 648. UPF 648 binds close to the FAD cofactor and perturbs the local active site structure, preventing productive binding of the substrate kynurenine
P38169
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6
7
-
purified recombinant enzyme, 4C, stable
8
-
-
purified recombinant enzyme, 4C, 10 h, loss of 21% of activity
9
-
-
purified recombinant enzyme, 4C, 10 h, loss of 32% of activity
10
-
-
purified recombinant enzyme, 4C, 3 h, complete inactivation
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
-
-
no loss of enzymatic activity after 24 hours
25
-
-
22% loss of enzymatic activity after 24 hours
37
-
-
stable for four hours
100
-
-
no enzymatic activity after boiling
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
purified recombinant enzyme is highly unstable, activity decreases directly after purification also at -80C
-, Q8ISJ5
disulfide reductants like dithiothreitol or 2-mercaptoethanol stabilize the enzyme
-
enzyme is protected against inactivation in the solubilized state by the presence of DTT, Triton X-100, and FAD in 0.1 M Tris-acetate buffer at pH 8.1
-
solubilized enzyme is appreciably stabilized in 0.05 M Tris-acetate buffer, pH 8.1, 1 mM DTT, 0.2 M mannitol, 0.2% Triton X-100, 0.005 mM FAD
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-80C, purified recombinant enzyme, not stable
-, Q8ISJ5
-70C no loss of enzymatic activity after 24 hours
-
-80C stable for 6 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant His-tagged enzyme from soluble fraction of Sf9 insect cells by nickel affinity chromatography
Q86PM2
recombinant enzyme from Sf9 insect cells by solubilization with Triton X-100 and affinity chromatography
-, Q8ISJ5
recombinant enzyme 8.8fold from Escherichia coli strain by ammonium sulfate fractionation and ion exchange chromatography to homogeneity
-
affinity chromatography
-
fusion protein with gluthatione-S-transferase
-
partial
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
gene kh, DNA and amino acid sequence analysis of wild-type and mutant genes, expression in Spodoptera frugiperda Sf9 cells as His-tagged, soluble protein via the baculovirus infection system
Q86PM2
AsK3H, DNA and amino acid sequence determination and analysis, functional expression in Spodoptera frugiperda Sf9 cells via the baculovirus infection system, membrane associated
-, Q8ISJ5
kinetic properties similar to the native liver enzyme
-
functional expression in Escherichia coli strain BL21 (DE3)
-
fusion protein with glutathione-S-transferase
-
expression in baculoviral system
P38169
DNA and amino acid sequence determnination and analysis, sequence comparisons, expression of FLAG-tagged wild-type enzyme and of C-terminal truncation mutants in COS-7 cells. The FLAG tag directs the wild-type enzyme to mitochondria but also to the cytosol and the plasma mambrane, overview
Q9MZS9
gene Tccn, homology-based cloning, DNA and amino acid sequence determination and analysis, gene structure analysis, the Tccn gene is located on linkage group 2
Q95NP6, -
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
Q86PM2
an inactive mutant lacks 162 nucleotides near the 3'-end of the mutant allele, the in-frame deletion results in loss of 54 amino acids leading to loss of enzyme activity and white eyes
additional information
Aedes aegypti Liverpool
-
an inactive mutant lacks 162 nucleotides near the 3'-end of the mutant allele, the in-frame deletion results in loss of 54 amino acids leading to loss of enzyme activity and white eyes
-
additional information
-
enzyme deficiency leads to the white eyes and white eggs w-1 phenotype in mutant silkworms, it can be partially rescued by expression of wild-type enzyme under control of either the cytoplasmic actin gene promoter, A3KMO, or the native KMO gene promoter, KKMO, phenotypes, overview
additional information
Bombyx mori C108
-
enzyme deficiency leads to the white eyes and white eggs w-1 phenotype in mutant silkworms, it can be partially rescued by expression of wild-type enzyme under control of either the cytoplasmic actin gene promoter, A3KMO, or the native KMO gene promoter, KKMO, phenotypes, overview
-
additional information
Q9MZS9
construction of C-terminal truncation mutants KMODELTAC10, KMODELTAC20, KMODELTAC30, KMODELTAC50, and KMODELTAC70, that are all localized in the cytosol after recombinant expression in COS-7 cells, exept for KMODELTAC10. Two forms of C-terminal truncation, KMODELTAC10D and KMODELTAC20D retain almost full activity but KMODELTAC30D shows 1.6fold higher activity than the wild-type. The activities of KMODELTAC50 and KMODELTAC70 is highly reduced, overview. The quantity of expressed KMODELTA30D in COS-7 cellsis 1.3fold higher than the wild-type KMO
additional information
Q95NP6, -
construction of mutants lacking functional enzyme via RNA interference, RNAi, the gene is unlinked to known eye-color mutants
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
molecular biology
-
wild-type KMO gene can be used as a marker gene for visually screening transgenic silkworms
molecular biology
Bombyx mori C108
-
wild-type KMO gene can be used as a marker gene for visually screening transgenic silkworms
-
analysis
-
comprehensive panel of biochemical and cell-based assays that use liquid chromatography/tandem mass spectrometry to quantify unlabeled kynurenine and 3-hydroxykynurenine and application to measure kynurenine monooxygenase inhibition in cell and tissue extracts, as well as cellular assays
medicine
-
enzyme is a therapeutical target for treatment of Huntigton disease
medicine
-
T helper 17 cells preferentially express kynurenine 3-monooxygenase. Enzyme inhibition, either with a specific inhibitor or via siRNA-mediated silencing, markedly increases IL-17 productionin vitro, whereas IFN-gamma production by T helper 1 cells is unaffected. Inhibition of kynurenine 3-monooxygenase significantly exacerbates disease in a Th17-driven model of autoimmune gastritis
medicine
-
the enzyme is an attractive target for the treatment of ischemic stroke
medicine
Pseudomonas fluorescens 17400
-
the enzyme is an attractive target for the treatment of ischemic stroke
-
molecular biology
Q95NP6, -
development of a transformant selection system for Tribolium castaneum on the basis of mutant rescue