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Information on EC 1.14.13.9 - kynurenine 3-monooxygenase and Organism(s) Homo sapiens
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1.14.13.9 kynurenine 3-monooxygenaseIUBMB Comments
A flavoprotein (FAD).
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Word Map
- 1.14.13.9
- mercury
- hg
-
kynurenic
- 3-hydroxykynurenine
-
quinolinic
-
2,3-dioxygenase
- kynureninase
- indoleamine
-
cronbach
- huntington
-
bartlett
-
paint
-
3-hydroxyanthranilic
-
quin
-
neuroactive
-
ochre
-
realgar
-
psychometric
-
calcite
- methylmercury
-
xanthurenic
-
eigenvalue
-
vermilion
-
hematite
-
test-retest
-
excitotoxins
-
ommochrome
-
artwork
-
geochemical
- indoleamine-2,3-dioxygenase
-
archaeological
-
varimax
-
roman
-
mineralogical
-
slovenia
-
micro-raman
- molecular biology
- medicine
- analysis
- pharmacology
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
cinnabar, kmo, kynurenine 3-monooxygenase, kynurenine 3-hydroxylase, kynurenine hydroxylase, kynurenine monooxygenase, kynurenine-3-monooxygenase, pfkmo, kyn-ohase, nadph-dependent flavin monooxygenase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
KMO
kynurenine 3-hydroxylase
-
-
-
-
kynurenine hydroxylase
kynurenine-3-monooxygenase
L-kynurenine-3-hydroxylase
-
-
-
-
oxygenase, kynurenine 3-mono-
-
-
-
-
kynurenine hydroxylase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-kynurenine + NADPH + H+ + O2 = 3-hydroxy-L-kynurenine + NADP+ + H2O
catalytic reaction mechanism, overview
L-kynurenine + NADPH + H+ + O2 = 3-hydroxy-L-kynurenine + NADP+ + H2O
the mechanism of L-Kyn catalysis by KMO is composed of reductive and oxidative half reactions. The binding of the substrate induces the reduction of FAD by NADH or by NADPH
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
L-kynurenine,NADPH:oxygen oxidoreductase (3-hydroxylating)
A flavoprotein (FAD).
CAS REGISTRY NUMBER
COMMENTARY
9029-61-2
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
the enzyme is involved in tryptophan catabolism
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
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
-
step in L-tryptophan catabolism, overview
-
-
?
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
?
-
following binding of L-KYN to KMO, NADPH acts as an electron donor and reduces FAD, leading to the formation of a L-KYN-FAD-hydroperoxide intermediate. L-KYN is then oxidised, resulting in the release of 3-HK and water
-
-
-
additional information
?
-
the mechanism of L-Kyn catalysis by KMO is composed of reductive and oxidative half reactions. The binding of the substrate induces the reduction of FAD by NADH or by NADPH. The initiation of FAD reduction is not unique to the substrate binding. It is also observed upon the binding of several inhibitors. The molecules that induce reduction of FAD other than the substrate are named as non-substrate effectors. Since the non-substrate effectors eliminate the hydroxyl transfer event but nonetheless initiate the formation of the FAD-hydroperoxide intermediate, they cause hydrogen peroxide formation. The triggering factor can arise from the substrate induced conformational changes in the loop above the isoalloxazine ring system
-
-
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
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
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
the enzyme is involved in tryptophan catabolism
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
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
-
step in L-tryptophan catabolism, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
KMO has an FAD cofactor, utilizes either NADPH or NADH, releases NADP+ /NAD+ after flavin reduction, and has one dinucleotide-binding domain. Rossmann fold simply characterizes a secondary structure with an alternating motif of beta sheets and alpha helices, and is of importance because this domain non-covalently binds the FAD cofactor and also contains the active site of the enzyme for KMO
-
FAD
cofactor flavin adenine dinucleotide (FAD) binds to KMO at a 1:1 ratio
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-cyclopentyl-N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)methanesulfonamide
-
-
2,2,2-trifluoro-N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)ethane-1-sulfonamide
-
-
2-(3,4-dichlorobenzoyl)-cyclopropane-1-carboxylic acid
UPF648, UPF648 prevents the binding of the native substrate KYN by binding closely to the FAD cofactor. In a transgenic Drosophila melanogaster model of Huntington's disease, UPF648 is shown to mitigate disease-relevant phenotypes. While UPF648 inhibits KMO, it also significantly increases the production of hydrogen peroxide by almost 20fold
-
2-(benzyloxy)-5-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid
-
-
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
Ro-61-8048, shows a greater potency than the previously discussed native substrate analogue 3,4-dichlorobenzoyl alanine
3,4-dimethoxy-N-[5-(3-nitrophenyl)-4-[(piperidin-1-yl)methyl]-1,3-thiazol-2-yl]benzene-1-sulfonamide
JM-6
-
3-(5-chloro-6-[(1R)-1-(pyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl)propanoic acid
GSK-065
-
3-[2-methylidene-5-(trifluoromethyl)-1,3-benzoxazol-3(2H)-yl]propanoic acid
-
3-[5-chloro-2-oxo-6-(propan-2-yl)-1,3-benzoxazol-3(2H)-yl]propanoic acid
-
3-[5-chloro-2-oxo-6-(trifluoromethyl)-1,3-benzoxazol-3(2H)-yl]propanoic acid
-
3-[5-chloro-2-oxo-6-[(propan-2-yl)oxy]-1,3-benzoxazol-3(2H)-yl]propanoic acid
-
3-[5-chloro-6-(cyclopropyloxy)-2-oxo-1,3-benzoxazol-3(2H)-yl]propanoic acid
-
4-amino-N-[4-(2-fluoro-5-trifluoromethyl-phenyl)-thiazol-2-yl]-benzenesulfonamide
-
-
4-chloro-2-([5-chloro-2-(5-methoxy-1,3-dihydro-2H-isoindol-2-yl)-1,3-thiazole-4-carbonyl](methyl)amino)-5-fluorobenzoic acid
-
-
4-methyl-N-(6-[2-(piperidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
permeable and strong KMO inhibitor
-
6-[3-(4-chloro-3-fluorophenyl)pyridin-2-yl]-1-methylquinazoline-2,4(1H,3H)-dione
-
-
6-[4-chloro-3-(cyclopropyloxy)phenyl]pyrimidine-4-carboxylic acid
CHDI-340246
-
ethyl (6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetate
KMO-inhibitor 1b, in the ligand structure, the carboxylate group of the inhibitor sits close to residues R83/Y97/N368 in the KMO active site. Several interactions between ligand and protein have been identified
-
ianthellamide A
an octopamine derivative isolated from the Australian marine sponge Ianthella quadrangulata, selectively inhibits KMO
-
N-(6-(5-fluoro-2-(piperidin-1-yl)phenyl)pyridazin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)methanesulfonamide
a brain-permeable and metabolically stable kynurenine monooxygenase inhibitor. The compound exhibits high brain permeability and a long-lasting pharmacokinetics profile in monkeys. Enzyme inhibition leads to production of neuroprotective kynurenic acid in the brain
-
N-(6-[2-fluoro-6-(piperidin-1-yl)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
-
-
N-(6-[3-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
-
-
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-1-(oxan-2-yl)methanesulfonamide
-
-
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-1-(oxan-3-yl)methanesulfonamide
-
-
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-1-(oxan-4-yl)methanesulfonamide
-
-
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-1-(oxolan-2-yl)methanesulfonamide
-
-
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-2-methoxyethane-1-sulfonamide
-
-
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-3-methoxypropane-1-sulfonamide
-
-
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
-
-
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)butane-2-sulfonamide
-
-
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)ethanesulfonamide
-
-
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)propane-1-sulfonamide
-
-
N-(6-[5-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
-
-
ZINC19827377
the inhibitor does not cause hydrogen peroxide as a harmful side product
-
ZINC71915355
the inhibitor is both blood brain barrier permeable and does not cause hydrogen peroxide as a harmful side product
-
(6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid
KMO-inhibitor 1
-
(6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid
KMO-inhibitor 1
-
3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
Ro 61-8048
-
3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
Ro 61-8048
-
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 molecular mechanism of action of three classes of inhibitors with differentiated binding modes and kinetics is reported. Two inhibitor classes trap the catalytic flavin in a tilting conformation. This correlates with picomolar affinities, increased residence times and an absence of the peroxide production
-
additional information
KMO inhibitors with brain permeability would be predicted to be more efficacious for treating neurodegenerative diseases than peripheral treatment, as inhibition of KMO in the CNS leads to increased neuroprotective KYNA levels as well as decreased levels of neurotoxic metabolites. Virtual screening combined with a prodrug strategy are used to develop brain-permeable KMO inhibitors. Prodrugs are considered as one of the most promising technologies for lead compound optimisation to cross the blood-brain barrier. For KMO inhibitors, one of the main challenges to cross the blood-brain barrier is the acidic centre, which mimics the binding of the carboxyl group of L-KYN
-
additional information
pyridazine derivatives as KMO inhibitors, structure-activity relationship, overview
-
additional information
determinations of inhibition with the purified enzyme and a cell-based assay
-
additional information
enzyme structure and ligand interaction analysis using the crystal structure of hKMO (PDB ID 5X68), library screening from Zinc15 database, detailed overview
-
additional information
research focuses on the inhibition of key enzymes in the kynurenine pathway (KP) to shunt it towards a neuroprotective state, based on the assumption that kynurenic acid (KYNA) has neuroprotective abilities. While substrate analogues bind in the active site of KMO and inhibit activity, they also detrimentally result in the formation of cytotoxic hydrogen peroxide by uncoupling the reaction of NAD(P)H and O2
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.153
L-kynurenine
pH 7, 37°C, full length 12His-tagged enzyme, FLAG tag removed during affinity purification
0.0087
NADPH
pH 7, 37°C, full length 12His-tagged enzyme, FLAG tag removed during affinity purification
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0001
(6-chloro-1H-indazol-1-yl)acetic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000286
1-cyclopentyl-N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)methanesulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000387
2,2,2-trifluoro-N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)ethane-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000038
2-(benzyloxy)-5-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid
Homo sapiens
pH 7.9, 37°C
-
0.0025
2-amino-3-(6-chloro-1H-indazol-1-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000034
3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.000037
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
Homo sapiens
pH and temperature not specified in the publication
0.02
3,4-dimethoxy-N-[5-(3-nitrophenyl)-4-[(piperidin-1-yl)methyl]-1,3-thiazol-2-yl]benzene-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0063
3-(1H-indazol-1-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000063
3-(5,6-dichloro-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000025
3-(5-chloro-1,2-benzoxazol-3-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.001
3-(5-chloro-1H-indazol-1-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000013
3-(5-chloro-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0001
3-(5-chloro-6-cyano-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000005
3-(5-chloro-6-ethoxy-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00001
3-(5-chloro-6-ethyl-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000013
3-(5-chloro-6-methoxy-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000013
3-(5-chloro-6-methyl-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000023
3-(5-chloro-6-[(1R)-1-(pyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl)propanoic acid
Homo sapiens
pH not specified in the publication, 37°C
-
0.000063
3-(5-chloro-7-methyl-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00063
3-(5-cyano-2-methylidene-1,3-benzoxazol-3(2H)-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.001
3-(5-methoxy-2-methylidene-1,3-benzoxazol-3(2H)-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000398
3-(6-bromo-1H-indazol-1-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0005
3-(6-chloro-1H-benzotriazol-1-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0006
3-(6-chloro-1H-indazol-1-yl)-2-hydroxypropanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0025
3-(6-chloro-1H-indazol-1-yl)-2-methylpropanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.005
3-(6-chloro-1H-indazol-1-yl)butanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00005
3-(6-chloro-1H-indazol-1-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00013
3-(6-chloro-1H-indol-1-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.002
3-(6-chloro-3-methyl-1H-indazol-1-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000079
3-(6-chloro-3-oxo-3,4-dihydro-2H-1-benzopyran-4-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0032
3-(6-methyl-1H-indazol-1-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.005
3-[2-methylidene-5-(trifluoromethyl)-1,3-benzoxazol-3(2H)-yl]propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00000071
3-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid
Homo sapiens
pH 7.9, 37°C
-
0.0001
3-[5-chloro-2-oxo-6-(propan-2-yl)-1,3-benzoxazol-3(2H)-yl]propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000398
3-[5-chloro-2-oxo-6-(trifluoromethyl)-1,3-benzoxazol-3(2H)-yl]propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000079
3-[5-chloro-2-oxo-6-[(propan-2-yl)oxy]-1,3-benzoxazol-3(2H)-yl]propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000032
3-[5-chloro-6-(cyclopropyloxy)-2-oxo-1,3-benzoxazol-3(2H)-yl]propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.003
4-(6-chloro-1H-indazol-1-yl)butanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000019
4-amino-N-[4-(2-fluoro-5-trifluoromethyl-phenyl)-thiazol-2-yl]-benzenesulfonamide
Homo sapiens
pH and temperature not specified in the publication
-
0.000014
4-chloro-2-([5-chloro-2-(5-methoxy-1,3-dihydro-2H-isoindol-2-yl)-1,3-thiazole-4-carbonyl](methyl)amino)-5-fluorobenzoic acid
Homo sapiens
pH 7.9, 37°C
-
0.0000024
4-methyl-N-(6-[2-(piperidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000068
6-[3-(4-chloro-3-fluorophenyl)pyridin-2-yl]-1-methylquinazoline-2,4(1H,3H)-dione
Homo sapiens
pH 7.9, 37°C
-
0.0000005
6-[4-chloro-3-(cyclopropyloxy)phenyl]pyrimidine-4-carboxylic acid
Homo sapiens
pH not specified in the publication, 37°C
-
0.0015
ianthellamide A
Homo sapiens
pH and temperature not specified in the publication
-
0.0000061
N-(6-[2-fluoro-6-(piperidin-1-yl)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.02
N-(6-[3-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000341
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-1-(oxan-2-yl)methanesulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000179
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-1-(oxan-3-yl)methanesulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000128
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-1-(oxan-4-yl)methanesulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.000041
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-1-(oxolan-2-yl)methanesulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000839
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-2-methoxyethane-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000616
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-3-methoxypropane-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000091
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000272
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)butane-2-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.000116
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)ethanesulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000371
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)propane-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000042
N-(6-[5-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
in first and second trimester of the placenta, within the fetal villus
-
especially in stromal and glandular epithelium in the first trimester decidua
additional information
an NADPH-dependent enzyme located in the outer mitochondrial membrane and linked to mitochondrial function, KMO is widely expressed in peripheral tissues, macrophages and monocytes
additional information
enzyme KMO is expressed in microglia and infiltrating macrophages in the brain, and at high levels in the liver, kidneys and placenta in the periphery
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
specifically, KMO is localised to the outer membrane of mitochondria where it associates with the lipid membrane using C-terminal transmembrane domains, which are also crucial for the catalytic activity of KMO
the C terminus of the enzyme contains a putative outer mitochondrial membrane-targeting sequence and this portion of the molecule is required enzyme function
KMO has two transmembrane domains, KMO is actually a single-pass transmembrane protein, with the other transmembrane domain lying laterally along the membrane, where it forms part of the ligand-binding pocket. Membrane-bound structure, overview
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug target
evolution
KMO belongs to a family of NAD(P)H-dependent flavin monooxygenase (FMO). KMO has one dicucleotide binding domain, which simply categorizes it as a Class A flavoprotein aromatic hydroxylase
malfunction
metabolism
physiological function
additional information
drug target
inhibition of the enzyme shows benefit in neurodegenerative diseases such as Huntingtons and Alzheimers. It is a target for acute pancreatitis multiple organ dysfunction syndrome
drug target
kynurenine represents a branch point of the kynurenine pathway, being converted into the neurotoxin 3-hydroxykynurenine via kynurenine monooxygenase, neuroprotectant kynurenic acid, and anthranilic acid. As a result of this branch point, kynurenine monooxygenase is an attractive drug target for several neurodegenerative and/or neuroinflammatory diseases, especially Huntington's, Alzheimer's, and Parkinson's diseases
drug target
the enzyme is a potential therapeutic target for neurodegenerative and neurologic disorders
drug target
the enzyme is a therapeutic target in several disease states, including Huntington's disease
malfunction
human polymorphism in the C-terminal region of the enzyme results in an Arg452Cys mutation, statistically linked to bipolar disorder and schizophrenia
malfunction
diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous lymphoid malignancy and a clinically heterogeneous lymphoid malignancy that is the most common type of lymphoma in Japan, patients with DLBCL have a poor progxadnosis due to increased levels of indoleamine 2,3-dioxygnase and kynurenine (KYN). Serum 3-hydroxy-L-kynurenine (3-HK) levels are regulated independently of serum KYN levels, and increased serum 3-HK levels and KMO activity are associated with worse disease progression. The addition of KMO inhibitors and 3-HK negatively and positively regulate the viability of DLBCL cells, respectively. NAD+ levels in high-KMO-expression-level KMOhigh STR-428 cells are significantly higher than those in low-KMO-expression-level KMOlow KML-1 cells. These results suggest that 3-HK generated by KMO activity may be involved in the regulation of DLBCL cell viability via NAD+ synthesis
malfunction
KMO is downregulated in autografts and is almost completely silenced in allograft rejection
malfunction
kynurenine-3-monooxygenase (KMO) is an important therapeutic target for several brain disorders. Potent inhibitors of KMO within different disease models show great therapeutic potential, especially in models of neurodegenerative disease. The inhibition of KMO reduces the production of downstream toxic kynurenine pathway metabolites and shifts the flux to the formation of the neuroprotectant kynurenic acid
malfunction
mutations at the dimeric interface abolish the enzyme activity
malfunction
neuroprotection of KMO inhibition through accumulation of kynureninic acid (KYNA) has neuroprotective effects and results in attenuation of NMDA receptor function
malfunction
the dysregulation of the kynurenine pathway and increased levels of toxic metabolites have been implicated in various disease states, including neurological disorders such as Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) epilepsy, affective disorders schizophrenia, depression, and anxiety, autoimmune related diseases rheumatoid arthritis (RA), multiple sclerosis (MS), and HIV-related dementia, peripheralconditions such as cardiovascular disease and ischemic stroke, and malignancies such as hematological neoplasia and colorectal cancer. The inhibition of KMO is a potential therapeutic strategy to rebalance the KP in hopes of mitigating and/or preventing disease progression since it sits at the key branching point of the KP. Inhibiting KMO will not only decrease the levels of toxic metabolites 3-HK and QUIN, but also increase the levels of the neuroprotective KYNA available for metabolism by kynurenine aminotransferase. Mechanisms, overview
metabolism
enzyme of the kynurenine pathway, which is the major catabolic route of tryptophan
metabolism
the enzyme is central to the kynurenine pathway of tryptophan metabolism
metabolism
the enzyme is involved in kynurenine pathway. It catalyzes the decisive step in production of metabolites as quinolinic acid
metabolism
FAD-dependent kynurenine 3-monooxygenase (KMO) catalyzes the conversion of L-kynurenine (L-Kyn) to 3-Hydroxykynurenine (3-HK) in the kynurenine pathway. In the pathway responsible for the catabolism of tryptophan, enzyme KMO regulates the levels of bioactive substances. L-Kyn, is also a substrate to both kynureninase (KYNU) and especially to kynurenine aminotransferase (KAT), which converts L-Kyn to kynurenic acid (KynA), a neuroprotective agent for being the antagonist of NMDA, alpha-7 nicotinic acetylcholine, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate, and an antioxidant for being the scavenger of several free radical species
metabolism
KMO is an important enzyme in the kynurenine pathway (KP), overview. The KP metabolises more than 95% of TRP. This pathway has been implicated in numerous diseases, including Huntington's disease, Alzheimer's disease, Parkinson's disease, schizophrenia, acute pancreatitis and cancer. L-kynurenine (L-KYN) can be metabolised by three different enzymes and lies at the key branchpoint of the KP. L-KYN can be metabolised to 3-hydroxy-L-kynurenine (3-HK) by KMO, or it can form kynurenic acid (KYNA), by a transamination reaction catalysed by kynurenine aminotransferase II (KATII), or alternatively it can be converted to anthranilic acid (AA) by kynureninase, which then feeds back into the 3-HK branch of the KP. Since KMO has the tightest binding affinity for L-KYN under normal conditions, the KMO branch has been considered to be the major metabolic route of the KP. KMO activity plays an essential role in maintaining a balance between the neurotoxic and neuroprotective potential of the pathway
metabolism
kynurenine 3-monooxygenase (KMO) catalyzes the conversion of L-kynurenine to 3-hydroxykynurenine (3-HK) in the kynurenine pathway (KP), the major route of tryptophan degradation in eukaryotic organisms
metabolism
the enzyme is involved in the kynurenine pathway (KP) that is the essential metabolic pathway for the catabolism of tryptophan. L-kynurenine (KYN) is the key and first stable intermediate of the KP by a formamidase. There are three possible metabolic fates for KYN, which involve biotransformations with (1) kynurenine aminotransferase (KAT) to form kynurenic acid (KynA), (2) kynureninase to form anthranilic acid, and (3) kynurenine 3-monooxygenase (KMO) to form 3-hydroxykynurnine (3-HK). 3-Hydroxykynurnine (3-HK) further leads to the formation of picolinic acid, 3-HANA, cinnabarinic acid, and quinolinic acid (QUIN). Three metabolites, QUIN, 3-HK, and 3-HANA, have been shown to be neurotoxic. KYNA serves as a neuroprotective agent due to its antagonistic effects at the glutamate receptor and all three subtypes of ionotropic receptors, N-methyl-D-aspartate (NMDA), kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA). KYNA selectively binds to a G-protein-coupled receptor, GPR35, leading to its activation. Also, kynurenic acid plays a role in epilepsy and has ability to reduce ischemic brain damage. KYNA also has antioxidant properties, as it can scavenge hydroxyl, superoxide anion, and other free radicals. Patients with schizophrenia presented with elevated kynurenic acid levels in the cerebral spinal fluid. Elevated levels of endogenous kynurenic acid increase the firing activity of midbrain dopamine neurons. This increase alters the effects of both nicotine and clozapine, leading to inhibitory responses of the ventral tegmental area (VTA) dopamine neurons that cause disrupted prepulse inhibition, an effect restored by antipsychotics. Elevated levels of KYNA have also been implicated in rapid progression among lung cancer patients, HIV-related illnesses, cataracts, tick-borne encephalitis, and partial seizures in epileptic patients. Most recently, KYNA has also been associated with antidepressant-like and antimigraine-like effects as well. Other endogenous neuroprotectant metabolites of the kynurenine pathway, detailed overview. Research focuse on the inhibition of key enzymes in the kynurenine pathway (KP) to shunt it towards a neuroprotective state, based on the assumption that kynurenic acid (KYNA) has neuroprotective abilities. Dissimilar to the other neurotoxic metabolites of the kynurenine pathway, the toxic effects of 3-hydroxykynurenine (3-HK) are independent of the NMDA receptor and solely result from the production of free radicals. 3-HK is mostly known for its ability to filter UV light in the human lens and its involvement in cataract formation. 3-HK is a controversial metabolite, while mostly considered neurotoxic, it is also able to act as a scavenger and is involved in immunoregulation. Similar to 3-HK, 3-hydroxyanthranilic acid (3-HANA) has also been shown to play a role in the regulation of the immune system and is believed to scavenge NO radicals. 3-HANA is prone to autooxidation
metabolism
the kynurenine pathway (KP) is the principal pathway for the metabolism of tryptophan (TRY) involving the enzyme, pathway overview
physiological function
KMO is a flavin-dependent hydroxylase that catalyzes the hydroxylation of L-kynurenine (L-Kyn) to 3-hydroxykynurenine (3-HK) in the kynurenine pathway (KP). The kynurenine pathway (KP) is the major mechanism for tryptophan catabolism with up to 99% of tryptophan being metabolized this way. Numerous pathological conditions involve KP, including neurological disorders (e.g., schizophrenia, depression, and anxiety), autoimmune diseases (e.g., multiple sclerosis and rheumatoid arthritis), peripheral conditions (e.g. cardiovascular disease and acute pancreatitis), and neurodegenerative illnesses (e.g., Huntington's disease, Alzheimer's disease, and Parkinson's disease) and HIV
physiological function
kynurenine 3-monooxygenase (KMO) catalyzes the conversion of L-kynurenine to 3-hydroxykynurenine (3-HK) in the kynurenine pathway (KP), the major route of tryptophan degradation in eukaryotic organisms. Kynurenine 3-monooxygenase (KMO), a key player in the kynurenine pathway (KP) of tryptophan degradation, regulates the synthesis of the neuroactive metabolites 3-hydroxykynurenine (3-HK) and kynurenic acid (KYNA). KMO activity is implicated in several major brain diseases including Huntington's disease (HD) and schizophrenia in humans
physiological function
kynurenine 3-monooxygenase (KMO) is a mitochondrial protein involved in the eukaryotic tryptophan catabolic pathway and is linked to various diseases
physiological function
kynurenine 3-monooxygenase (KMO) regulates the levels of bioactive substances in the kynurenine pathway of tryptophan catabolism and its activity is tied to many diseases. The product of the enzyme reaction, 3-hydroxy-L-kynurenine (3-HK), is a neurotoxic agent that induces apoptosis and damages wide range of cell types. It is further converted to the free-radical generator 3-hydroxyanthranilate (3-HanA) which is then converted to the selective N-methyl-D-aspartate (NMDA) receptor agonist quinolinate. High levels of these substances correlate with the neurodegenerative diseases (Huntington's, Alzheimer's, and Parkinson's)
physiological function
kynurenine-3-monooxygenase (KMO) is an enzyme that relies on nicotinamide adenine dinucleotide phosphate (NADP), a key site in the kynurenine pathway (KP), which has great effects on neurological diseases, cancer, and peripheral inflammation. Enzyme controlling the chief division of the KP, which directly controls downstream product quinolinic acid (QUIN) and indirectly controls kynurenic acid (KYNA), plays an important role in many diseases, especially neurological diseases. Role of KMO in different neurological diseases, such as Huntington's disease, schizophrenia, ischemic stroke and neuropathic headache, Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis, as well as in non-neurological diseases, such as acute pancreatitis and hepatocellular carcinoma, mechanisms, detailed overview
physiological function
renal tubular epithelial cells (TECs) are the primary targets of ischemia-reperfusion injury (IRI) and rejection by the recipient's immune response in kidney transplantation (KTx). Kynurenine 3-monooxygenase (KMO) and kynureninase are reduced in ischemia-reperfusion procedure, molecular mechanism, overview. TEC injury in acutely rejection allografts is associated with alterations of Bcl2 family proteins, reduction of tight junction protein 1 (TJP1), and TEC-specific KMO. Three cytokines, IFNgamma, TNFalpha, and IL1beta, aere identified as triggers of TEC injury by altering the expression of Bcl2, BID, and TJP1. Allograft rejection and TEC injury are always associated with a dramatic reduction of KMO. 3-Hydroxy-L-kynurenine (3HK) and hydroxyl-3 anthranilic acid (3HAA) as direct and downstream products of KMO, effectively protect TEC from injury via increasing expression of Bcl-xL and TJP1. 3HK and 3HAA effectively inhibit T cell proliferation
physiological function
viability of diffuse large B-cell lymphoma cells is regulated by kynurenine 3-monooxygenase activity
additional information
a Rossmann fold simply characterizes a secondary structure with an alternating motif of beta sheets and alpha helices, and is of importance because this domain non-covalently binds the FAD cofactor and also contains the active site of the enzyme for KMO
additional information
analysis of the extended ligand-binding pocket of in meso KMO and its binding mode
additional information
structure comparisons with the enzymes from Saccharomyces cerevisiae (scKMO) and Pseudomonas fluorescens (pfKMO), overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). KMO_HUMAN
486
2
55810
Swiss-Prot
other Location (Reliability: 5)
A0A024R3S9_HUMAN
526
2
60237
TrEMBL
Mitochondrion (Reliability: 3)
Q9BS61_HUMAN
407
0
46569
TrEMBL
other Location (Reliability: 5)
A8K693_HUMAN
486
2
55717
TrEMBL
other Location (Reliability: 5)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
the structure of KMO can be realized as three domains: the first domain is where FAD is buried within beta-sheets and alpha-helices, one of which is the long alpha-helix that leads to the C-terminal domain. This helix and a loop that stands above the isoalloxazine rings of FAD define the borders of the active site in this region. The second region contains the residues of alpha-helices and beta-sheets whose side chains set the final border to the active site. Therefore, the active site is contained at the interface of the first and second regions. The third region of PfKMO consists of four alpha-helices while in scKMO and hKMO there are only the two alpha-helices of the transmembrane domain
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified full-length structure of KMO in its membrane-embedded form, complexed with 2-(benzyloxy)-5-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid and 4-chloro-2-([5-chloro-2-(5-methoxy-1,3-dihydro-2H-isoindol-2-yl)-1,3-thiazole-4-carbonyl](methyl)amino)-5-fluorobenzoic acid at 3.0 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E366Q
2% of the enzyme activity compared with that of the wild-type enzyme
M367A
2% of the enzyme activity compared with that of the wild-type enzyme
M367L
13% of the enzyme activity compared with that of the wild-type enzyme
N363A
28% of the enzyme activity compared with that of the wild-type enzyme
N465A
about 80% of the enzyme activity compared with that of the wild-type enzyme
R85K
1% of the enzyme activity compared with that of the wild-type enzyme
Y398A
1% of the enzyme activity compared with that of the wild-type enzyme
Y398F
1% of the enzyme activity compared with that of the wild-type enzyme
Y99F
7% of the enzyme activity compared with that of the wild-type enzyme
additional information
additional information
the enzyme is systematically truncated according to the sequence alignments and the predicted secondary structures. For the truncations 1-377, 1-379, and 1-394, which have 1 or 2 more predicted alpha-helices than that of the 1-372/374, no or weak protein expression is detected. Although for the truncation 1-430 that has the C-terminal hydrophobic tail removed, no enzymatic activities can be detected but the protein expression is normal. The results indicate that the C-terminal portion is important for both the folding and the enzymatic activity
additional information
-
the enzyme is systematically truncated according to the sequence alignments and the predicted secondary structures. For the truncations 1-377, 1-379, and 1-394, which have 1 or 2 more predicted alpha-helices than that of the 1-372/374, no or weak protein expression is detected. Although for the truncation 1-430 that has the C-terminal hydrophobic tail removed, no enzymatic activities can be detected but the protein expression is normal. The results indicate that the C-terminal portion is important for both the folding and the enzymatic activity
additional information
generation of a C-terminal domain truncated human KMO whose membrane targeting sequence in its C-terminal domain is suggested to be an essential part of its catalysis
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene kmo, quantitative reverse transcription-PCR enzyme expression analysis
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
KMO is downregulated in autografts and is almost completely silenced in allograft rejection
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
diagnostics
the upregulation of KMO currently serves as an independent prognostic biomarker to identify certain liver malignancies, particularly hepatocellular carcinoma (HCC). HCC patients who express increased KMO activity are known to have unfavorable clinical outcomes compared to those who do not. The upregulation of KMO also plays a critical role in triple-negative breast cancer progression and metastasis. The pharmacological inhibition of KMO with GSK180 granted therapeutic protection in acute pancreatitis rodent models preventing multiple organ failures
drug development
medicine
pharmacology
kynurenine represents a branch point of the kynurenine pathway, being converted into the neurotoxin 3-hydroxykynurenine via kynurenine monooxygenase, neuroprotectant kynurenic acid, and anthranilic acid. As a result of this branch point, kynurenine monooxygenase is an attractive drug target for several neurodegenerative and/or neuroinflammatory diseases, especially Huntington's, Alzheimer's, and Parkinson's diseases
drug development
enzyme KMO is an important drug target due to its role in regulating the levels of bioactive substances with contrasting effects. For treatment of central nervous related diseases, it is required that enzyme inhibitors should be both blood brain barrier permeable and should not cause hydrogen peroxide as a harmful side product. Molecular dynamics simulations and MM/GBSA calculations, overview
drug development
importance of KMO as a drug target in neurological disease, benefits of brain permeable inhibitors in modulating kynurenine pathway metabolites in the central nervous system teeating brain neurological diseases
drug development
the enzyme is a target for drug development in neurological, but also other, diseases, pharmacophore development with receptor-based pharmacophore modeling, detailed overview
medicine
inhibition of the enzyme shows benefit in neurodegenerative diseases such as Huntington's and Alzheimer's. It is a target for acute pancreatitis multiple organ dysfunction syndrome
medicine
the enzyme is a potential therapeutic target for neurodegenerative and neurologic disorders
medicine
importance of KMO as a drug target in neurological disease, benefits of brain permeable inhibitors in modulating kynurenine pathway metabolites in the central nervous system teeating brain neurological diseases. KMO inhibitors with brain permeability would be predicted to be more efficacious for treating neurodegenerative diseases than peripheral treatment, as inhibition of KMO in the CNS leads to increased neuroprotective KYNA levels as well as decreased levels of neurotoxic metabolites
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Saito, K.; Quearry, B.J.; Saito, M.; Nowak, T.S.Jr.; Markey S.P.; Heyes, M.P.
Kynurenine 3-hydroxylase in brain: species activity differences and effect of gerbil cerebral ischemia
Arch. Biochem. Biophys.
307
104-109
1993
Homo sapiens, Macaca mulatta, Meriones unguiculatus, Mus musculus, Rattus norvegicus
Drysdale, M.J.; Hind, S.L.; Jansen, M.; Reinhard, J.F.Jr
Synthesis and SAR of 4-aryl-2-hydroxy-4-oxobut-2-enoic acids and esters and 2-amino-4-aryl-4-oxobut-2-enoic acids and esters: Potent inhibitors of kynurenine-3-hydroxylase as potential neuroprotective agents
J. Med. Chem.
43
123-127
2000
Homo sapiens
Alberati-Giani, D.; Cesuura, A.M.; Broger, C.; Warren, W.D.; Rover, S.; Malherbe, P.
Cloning and functional expression of human kynurenine 3-monooxygenase
FEBS Lett.
410
407-412
1997
Homo sapiens
Giorgini, F.; Guidetti, P.; Nguyen, Q.; Bennett, S.C.; Muchowski, P.J.
A genomic screen in yeast implicates kynurenine 3-monooxygenase as a therapeutic target for Huntington disease
Nat. Genet.
37
526-531
2005
Saccharomyces cerevisiae, Homo sapiens
Ligam, P.; Manuelpillai, U.; Wallace, E.M.; Walker, D.
Localisation of indoleamine 2,3-dioxygenase and kynurenine hydroxylase in the human placenta and decidua: implications for role of the kynurenine pathway in pregnancy
Placenta
26
498-504
2005
Homo sapiens
Winkler, D.; Beconi, M.; Toledo-Sherman, L.M.; Prime, M.; Ebneth, A.; Dominguez, C.; Munoz-Sanjuan, I.
Development of LC/MS/MS, high-throughput enzymatic and cellular assays for the characterization of compounds that inhibit kynurenine monooxygenase (KMO)
J. Biomol. Screen.
18
879-889
2013
Homo sapiens
Liddle, J.; Beaufils, B.; Binnie, M.; Bouillot, A.; Denis, A.A.; Hann, M.M.; Haslam, C.P.; Holmes, D.S.; Hutchinson, J.P.; Kranz, M.; McBride, A.; Mirguet, O.; Mole, D.J.; Mowat, C.G.; Pal, S.; Rowland, P.; Trottet, L.; Uings, I.J.; Walker, A.L.; Webster, S.P.
The discovery of potent and selective kynurenine 3-monooxygenase inhibitors for the treatment of acute pancreatitis
Bioorg. Med. Chem. Lett.
27
2023-2028
2017
Homo sapiens (O15229)
Smith, J.R.; Jamie, J.F.; Guillemin, G.J.
Kynurenine-3-monooxygenase a review of structure, mechanism, and inhibitors
Drug Discov. Today
21
315-324
2016
Homo sapiens (O15229), Rattus norvegicus (O88867), Pseudomonas fluorescens (Q84HF5), Sus scrofa (Q9MZS9)
Gao, J.; Yao, L.; Xia, T.; Liao, X.; Zhu, D.; Xiang, Y.
Biochemistry and structural studies of kynurenine 3-monooxygenase reveal allosteric inhibition by Ro 61-8048
FASEB J.
32
2036-2045
2017
Homo sapiens (O15229), Homo sapiens, Pseudomonas fluorescens (Q84HF5), Pseudomonas fluorescens
Hutchinson, J.P.; Rowland, P.; Taylor, M.R.D.; Christodoulou, E.M.; Haslam, C.; Hobbs, C.I.; Holmes, D.S.; Homes, P.; Liddle, J.; Mole, D.J.; Uings, I.; Walker, A.L.; Webster, S.P.; Mowat, C.G.; Chung, C.W.
Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase
Nat. Commun.
8
15827
2017
Homo sapiens (O15229), Pseudomonas fluorescens (Q84HF5)
Gonzalez Esquivel, D.; Ramirez-Ortega, D.; Pineda, B.; Castro, N.; Rios, C.; Perez de la Cruz, V.
Kynurenine pathway metabolites and enzymes involved in redox reactions
Neuropharmacology
112
331-345
2017
Homo sapiens (O15229), Rattus norvegicus (O88867)
Wilson, K.; Mole, D.; Binnie, M.; Homer, N.; Zheng, X.; Yard, B.; Iredale, J.; Auer, M.; Webster, S.
Bacterial expression of human kynurenine 3-monooxygenase Solubility, activity, purification
Protein Expr. Purif.
95
96-103
2014
Homo sapiens (O15229), Homo sapiens
Sathyasaikumar, K.V.; Perez de la Cruz, V.; Pineda, B.; Vazquez Cervantes, G.I.; Ramirez Ortega, D.; Donley, D.W.; Severson, P.L.; West, B.L.; Giorgini, F.; Fox, J.H.; Schwarcz, R.
Cellular localization of kynurenine 3-monooxygenase in the brain challenging the dogma
Antioxidants (Basel)
11
0000
2022
Homo sapiens (A0A024R3S9), Mus musculus (Q91WN4)
Zhang, S.; Collier, M.E.W.; Heyes, D.J.; Giorgini, F.; Scrutton, N.S.
Advantages of brain penetrating inhibitors of kynurenine-3-monooxygenase for treatment of neurodegenerative diseases
Arch. Biochem. Biophys.
697
108702
2021
Homo sapiens (A0A024R3S9), Rattus norvegicus (O88867), Mus musculus (Q91WN4)
Tsuboi, K.; Kimura, H.; Nakatsuji, Y.; Kassai, M.; Deai, Y.; Isobe, Y.
Discovery of N-(6-(5-fluoro-2-(piperidin-1-yl)phenyl)pyridazin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)methanesulfonamide as a brain-permeable and metabolically stable kynurenine monooxygenase inhibitor
Bioorg. Med. Chem. Lett.
44
128115
2021
Homo sapiens (O15229), Mus musculus (Q91WN4), Mus musculus
Mimasu, S.; Yamagishi, H.; Kubo, S.; Kiyohara, M.; Matsuda, T.; Yahata, T.; Thomson, H.A.; Hupp, C.D.; Liu, J.; Okuda, T.; Kakefuda, K.
Full-length in meso structure and mechanism of rat kynurenine 3-monooxygenase inhibition
Commun. Biol.
4
159
2021
Homo sapiens (O15229), Rattus norvegicus (O88867)
Lu, Y.; Shao, M.; Wu, T.
Kynurenine-3-monooxygenase a new direction for the treatment in different diseases
Food Sci. Nutr.
8
711-719
2020
Homo sapiens (O15229)
Lassiter, R.; Merchen, T.D.; Fang, X.; Wang, Y.
Protective role of kynurenine 3-monooxygenase in allograft rejection and tubular injury in kidney transplantation
Front. Immunol.
12
671025
2021
Homo sapiens (O15229), Sus scrofa (Q9MZS9), Sus scrofa
Oezkilic, Y.; Tuezuen, N.S.
In silico methods predict new blood-brain barrier permeable structure for the inhibition of kynurenine 3-monooxygenase
J. Mol. Graph. Model.
100
107701
2020
Homo sapiens (O15229), Saccharomyces cerevisiae (P38169), Pseudomonas fluorescens (Q84HF5)
Hughes, T.D.; Guener, O.F.; Iradukunda, E.C.; Phillips, R.S.; Bowen, J.P.
The kynurenine pathway and kynurenine 3-monooxygenase inhibitors
Molecules
27
273
2022
Homo sapiens (O15229), Saccharomyces cerevisiae (P38169), Pseudomonas fluorescens (Q84HF5), Mus musculus (Q91WN4)
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