1.13.11.52: indoleamine 2,3-dioxygenase
This is an abbreviated version!
For detailed information about indoleamine 2,3-dioxygenase, go to the full flat file.
Word Map on EC 1.13.11.52
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1.13.11.52
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kynurenine
-
dendritic
-
t-cells
-
lymphocyte
-
immunotherapy
-
ifn-gamma
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immunomodulatory
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autoimmune
-
mesenchymal
-
interferon-gamma
-
tregs
-
allogeneic
-
immunoregulatory
-
rejection
-
serotonin
-
heme
-
monocyte
-
tolerogenic
-
quinolinic
-
checkpoint
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neopterin
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allograft
-
immunomodulation
-
foxp3
-
antigen-presenting
-
immunoregulation
-
myeloid-derived
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3-hydroxykynurenine
-
ctla-4
-
graft-versus-host
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l-trp
-
3-hydroxyanthranilic
-
quin
-
tumor-infiltrating
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heme-containing
-
depressive-like
-
immunotherapeutic
-
plasmacytoid
-
5-hydroxytryptamine
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monocyte-derived
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ifn-gamma-induced
-
5-hydroxyindoleacetic
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interferon-gamma-induced
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immuno-oncology
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drug development
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cd4+cd25+foxp3+
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mdscs
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pharmacology
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alloreactive
-
3-monooxygenase
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ifn-gamma-mediated
-
medicine
-
death-ligand
-
synthesis
- 1.13.11.52
- kynurenine
- dendritic
- t-cells
- lymphocyte
-
immunotherapy
- ifn-gamma
-
immunomodulatory
- autoimmune
- mesenchymal
- interferon-gamma
-
tregs
-
allogeneic
-
immunoregulatory
-
rejection
- serotonin
- heme
- monocyte
-
tolerogenic
-
quinolinic
-
checkpoint
- neopterin
-
allograft
-
immunomodulation
- foxp3
-
antigen-presenting
-
immunoregulation
-
myeloid-derived
- 3-hydroxykynurenine
-
ctla-4
- graft-versus-host
- l-trp
-
3-hydroxyanthranilic
-
quin
-
tumor-infiltrating
-
heme-containing
-
depressive-like
-
immunotherapeutic
-
plasmacytoid
- 5-hydroxytryptamine
-
monocyte-derived
-
ifn-gamma-induced
-
5-hydroxyindoleacetic
-
interferon-gamma-induced
-
immuno-oncology
- drug development
-
cd4+cd25+foxp3+
-
mdscs
- pharmacology
-
alloreactive
-
3-monooxygenase
-
ifn-gamma-mediated
- medicine
-
death-ligand
- synthesis
Reaction
Synonyms
31854, BRAFLDRAFT_126354, CG5163, EC 1.13.1.12, hIDO, hIDO1, hTDO, IDO, IDO-1, IDO-2, IDO-I, IDO-II, IDO-III, IDO-IV, IDO1, IDO2, INDO, INDOL1, indolamine 2,3-dioxygenase, indole 2,3-dioxygenase, indoleamine 2, 3-dioxygenase, indoleamine 2,3 dioxygenase, indoleamine 2,3-dioxygenase, indoleamine 2,3-dioxygenase 1, indoleamine 2,3-dioxygenase 2, indoleamine 2,3-dioxygenase-1, indoleamine 2,3-dioxygenase-2, indoleamine 2,3-dioxygenase-like protein, indoleamine-2,3-dioxygenase, Indoleamine-pyrrole 2,3-dioxygenase, L-tryptophan 2,3-dioxygenase, L-tryptophan pyrrolase, mIDO, oxygenase, tryptophan 2,3-di-, proto-IDO, proto-indoleamine 2,3-dioxygenase, superoxygenase, TDO, TDO2, TioF, TO, TRPO, Tryptamin 2,3-dioxygenase, tryptamine 2,3-dioxygenase, tryptophan 2,3-dioxygenase, tryptophan dioxygenase, tryptophan oxygenase, tryptophan peroxidase, tryptophan pyrrolase, tryptophan-2,3-dioxygenase, tryptophanase, v1g244579, Vermilion protein
ECTree
1.13.11.52 indoleamine 2,3-dioxygenaseAdvanced search results
results (
results (Substrates Products
Substrates Products on EC 1.13.11.52 - indoleamine 2,3-dioxygenase
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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
1-benzofuran-DL-tryptophan + O2
?
-
1 mM, 22% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
1-benzothiophene-DL-tryptophan + O2
?
-
1 mM, 19% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
1-methyl-DL-tryptophan + O2
?
-
1 mM, 7% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
2-bromo-L-tryptophan + O2
?
-
1 mM, 21% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
2-chloro-L-tryptophan + O2
?
-
1 mM, 33% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
2-hydroxy-L-tryptophan + O2
?
-
1 mM, 4% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
4-methyl-DL-tryptophan + O2
?
-
1 mM, 33% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
5-benzyloxy-DL-tryptophan + O2
?
-
1 mM, 1% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
5-bromo-DL-tryptophan + O2
?
-
1 mM, 36% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
5-fluoro-DL-tryptophan + O2
5-fluoro-N-formyl-DL-kynurenine
-
-
-
?
5-fluoro-tryptophan + O2
4-(2-amino-5-fluorophenyl)-2-(formylamino)-4-oxobutanoic acid
-
-
-
?
5-hydroxy-L-tryptophan + O2
(2S)-4-(2-amino-5-hydroxyphenyl)-2-(formylamino)-4-oxobutanoic acid
5-hydroxy-tryptophan + O2
4-(2-amino-5-hydroxyphenyl)-2-(formylamino)-4-oxobutanoic acid
-
-
-
?
5-methoxy-D,L-tryptophan + O2
?
-
1 mM, 70% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
5-methoxy-DL-tryptophan + O2
5-methoxy-N-formyl-DL-kynurenine
-
-
-
?
5-methyl-D,L-tryptophan + O2
?
-
1 mM, 123% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
5-methyl-tryptophan + O2
4-(2-amino-5-methylphenyl)-2-(formylamino)-4-oxobutanoic acid
-
-
-
?
6-methyl-DL-tryptophan + O2
6-methyl-N-formyl-DL-kynurenine
-
-
-
?
6-nitro-L-tryptophan + O2
?
-
1 mM, 2% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
7-methyl-DL-tryptophan + O2
?
-
1 mM, 18% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
alpha-methyl-DL-tryptophan + O2
?
-
1 mM, 35% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
alpha-N-methyl-L-tryptophan + O2
?
-
1 mM, 21% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
beta-methyl-DL-tryptophan + O2
?
-
1 mM, 32% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
DL-alpha-methyltryptophan + O2
alpha-methyl-N-formyl-DL-kynurenine
-
9.0% of the activity with L-Trp
-
-
?
indole-3-propionic acid + O2
?
altered kinetics for IPA (very long lag phase) as being consistent with a role for the ammonium group in stabilizing the ferric superoxide complex (via the radical pathway). The rate-limiting steps are different from the other substrates examined so that Compound II does not accumulate, but product formation is still possible, product formation ananlysis by LC-MS
-
-
?
L-tryptophan ethyl ester + O2
?
-
1 mM, 14% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
L-tryptophan methyl ester + O2
?
-
1 mM, 15% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
N-acetyl-L-tryptophan + O2
?
-
1 mM, 3% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
tryptophan + O2
N-formylkynurenine
-
if the cellular environment protects indoleamine 2,3-dioxygenase from oxidation to the ferric form, no additional electron donor might by required for indolamine 2,3-dioxygenase activity in intact tissues
-
-
?
5-fluoro-DL-tryptophan + O2
?
-
1 mM, 46% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
5-hydroxy-L-tryptophan + O2
(2S)-4-(2-amino-5-hydroxyphenyl)-2-(formylamino)-4-oxobutanoic acid
-
-
-
?
5-hydroxy-L-tryptophan + O2
(2S)-4-(2-amino-5-hydroxyphenyl)-2-(formylamino)-4-oxobutanoic acid
-
-
-
-
?
5-hydroxy-L-tryptophan + O2
5-hydroxy-N-formyl-L-kynurenine
-
-
-
?
5-hydroxy-L-tryptophan + O2
?
-
1 mM, 59% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
5-hydroxy-L-tryptophan + O2
N-formyl-5-hydroxy-L-kynurenine
-
-
-
-
?
5-methyl-DL-tryptophan + O2
5-methyl-N-formyl-DL-kynurenine
-
-
-
?
5-methyl-DL-tryptophan + O2
5-methyl-N-formyl-DL-kynurenine
high activity
-
-
?
6-fluoro-DL-tryptophan + O2
?
-
1 mM, 38% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
6-methyl-DL-tryptophan + O2
?
-
1 mM, 72% activity relative to L-tryptophan, 50 mM potassium phosphate, pH 6.5, 10 mM ascorbic acid, 0.01 mM methylene blue, 0.1 mg catalase, 37°C, 10 min
-
-
?
D-Trp + O2
N-formyl-D-kynurenine
-
0.7% of the activity with L-Trp
-
-
?
D-tryptophan + O2
N-formyl-D-kynurenine
-
-
-
-
?
D-tryptophan + O2
N-formyl-D-kynurenine
-
the initial deprotonation reaction of the indole NH group in hTDO is carried out by the evolutionarily conserved distal His. stereospecificity of hTDO is determined by the efficiency of the dioxygen chemistry
-
-
?
D-tryptophan + O2
N-formyl-D-kynurenine
IDO displays a similar kcat for D- and L-tryptophan, but D-tryptophan has 173folds higher Km
-
-
?
D-tryptophan + O2
N-formyl-D-kynurenine
-
L-Trp is a better substrate for IDO than D-Trp
-
-
?
D-tryptophan + O2
N-formyl-D-kynurenine
D-Trp is a substrate of hIDO1 but has very low affinity
-
-
?
D-tryptophan + O2
N-formyl-D-kynurenine
-
-
-
-
?
D-tryptophan + O2
N-formyl-D-kynurenine
-
-
-
-
?
D-tryptophan + O2
N-formyl-D-kynurenine
-
O2- binds first to the ferric enzyme and is followed by rapid binding of L-tryptophan
-
-
?
D-tryptophan + O2
N-formyl-D-kynurenine
while L and D-tryptophan have similar affinities (Km values), the kcat is 10times lower for D-tryptophan
-
-
?
DL-5-fluoro-methyltryptophan + O2
?
-
35% of the activity with L-Trp
-
-
?
DL-5-fluoro-methyltryptophan + O2
?
-
30.6% of the activity with L-Trp
-
-
?
L-Trp + O2
L-formylkynurenine
during larval life the enzyme controls the level of potentially harmful free Trp in the hemolymph by converting it to kynurenine, and during adult development the enzyme catalyzes the first step of brown eye pigment biosynthesis
-
-
?
L-Trp + O2
L-formylkynurenine
-
lipopolysaccharide and muramyl tripeptide upregulate enzyme induction through a mechanism independent of interleukin 1alpha
-
-
?
L-Trp + O2
L-formylkynurenine
-
interleukin-4 inhibits expression of the enzyme in monocytes
-
-
?
L-Trp + O2
L-formylkynurenine
-
initial enzyme of tryptophan degradation pathway
-
-
?
L-Trp + O2
L-formylkynurenine
-
activity is increased in important biological processes, such as protection of the fetus from rejection during pregnancy and possibly T cell death in HIV-infected patients
-
-
?
L-Trp + O2
L-formylkynurenine
-
Trp degradation by the enzyme regulates lymphocyte proliferation
-
-
?
L-Trp + O2
L-formylkynurenine
rate-limiting enzyme in the catabolism of tryptophan
-
-
?
L-Trp + O2
L-formylkynurenine
-
IDO is the first enzyme in UV-filter pathway. UV-filter biosynthesis is active even in aged lenses
-
-
?
L-Trp + O2
L-formylkynurenine
-
the enzyme inhibits tumor cell proliferation by tryptophan depletion. IDO-induced suppression of antitumoral immune response in both adenocarcinoma and squamous cell carcinoma
-
-
?
L-Trp + O2
L-formylkynurenine
-
proposed reaction mechanism involves the proton abstraction by iron-bound dixoygen. The O-O bond is precisely controlled by the heme proximal and distal environment and is not cleaved before the incorporation of both oxygen atoms into the substrate
-
-
?
L-Trp + O2
L-formylkynurenine
-
indoleamine 2,3-dioxygenase has almost no detectable activity at or below 0.1 mM oxygen and maximum activity at about 1.15 mM
-
?
L-Trp + O2
L-formylkynurenine
-
indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase catalyze the rate-limiting step in the kynurenine pathway from Trp to quinolinic acid
-
-
?
L-Trp + O2
L-formylkynurenine
-
enzyme contributes to tumor cell evasion of T cell-mediated rejection
-
-
?
L-Trp + O2
L-formylkynurenine
-
expression of indoleamine 2,3-dioxygenase is an inducible feature of specific subsets of dendritic cells, and provides a potential mechanistic explanation for their T cell regulatory properties
-
-
?
L-Trp + O2
L-formylkynurenine
-
enzyme from liver is specific for L-Trp, the enzyme from brain is active with L-Trp and D-Trp, the enzyme from lung is active with L-Trp and D-5-hydroxytryptophan
-
?
L-Trp + O2
L-formylkynurenine
-
superoxide anion is required for the initiation of the reaction and the maintenance of the catalytic cycle during the steady state
-
?
L-Trp + O2
L-formylkynurenine
-
tryptophan-derived catabolites are responsible for inhibition of T cell and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase
-
-
?
L-Trp + O2
L-formylkynurenine
-
a dramatic and specific induction of the pulmonary enzyme by virus and lipopolysaccharide is mediated by interferon. The enzyme may play an important role in the inflammatory processes, immune responses, and/or the mode of action of interferon
-
-
?
L-Trp + O2
L-formylkynurenine
-
influenza virus infection and tumor transplantation induce the enzyme
-
-
?
L-Trp + O2
L-formylkynurenine
-
absolutely specific for L-Trp
-
?
L-Trp + O2
L-formylkynurenine
-
absolutely specific for L-Trp
-
?
L-Trp + O2
L-formylkynurenine
-
enzyme from liver is specific for
-
?
L-Trp + O2
L-formylkynurenine
-
tryptophan 2,3-dioxygenase activity is appreciable even at 0.03 mM oxygen and rises steeply to a maximum at 0.04 mM
-
?
L-Trp + O2
L-formylkynurenine
-
indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase catalyze the rate-limiting step in the kynurenine pathway from Trp to quinolinic acid
-
-
?
L-Trp + O2
L-formylkynurenine
-
enzyme controls the physiological flux of Trp into both the serotonergic and kynureninic pathways
-
-
?
L-Trp + O2
L-formylkynurenine
-
key enzyme of tryptophan catabolism, importance as regulator of whole-body tryptophan catabolism and brain levels of tryptophan and serotonin
-
-
?
L-Trp + O2
L-formylkynurenine
-
the skin enzyme may play an important role in the initiation or suppression of rat hair growth
-
-
?
L-Trp + O2
L-formylkynurenine
-
key regulatory enzyme, though irreversible degradation, controls the flux of tryptophan through physiologically relevant pathways
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
tryptophan indirectly activates TDO through promoting the production of reactive oxygen species
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
-
tryptophan 2,3-dioxygenase is the only enzyme able to initiate L-tryptophan degradation through the kynurenine pathway
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
Glu132 in Blepharisma IDO-III is crucial for its high affinity for L-Trp. No activity with 5-hydroxy-L-tryptophan
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
no activity with 5-hydroxy-L-tryptophan
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
-
the enzyme is involved in tryptophan catabolism and in quinolinate biosynthesis
-
-
ir
L-tryptophan + O2
N-formyl-L-kynurenine
enzyme shows induced-fit mechanism to bind L-Trp, two conserved but flexible loops undergo conformational changes, converting the active site from an open conformation to a closed conformation, key residues involved in recognition and binding of the heme and the substrate, Molecular modeling and dynamics simulation, overview
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
-
-
395463, 395469, 395472, 657496, 659233, 660498, 663910, 664443, 665164, 666239, 666378, 666763, 666895, 671990, 685239
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
-
-
687116, 687297, 687590, 696151, 700405, 711247, 711422, 711580, 711776, 711952, 712112, 712172, 712173, 712230, 712250, 712647, 712820, 712832, 712945, 712947, 713489, 724912
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
-
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
-
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
no activity with D-tryptophan
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
-
plays an important role in the immune response by catalyzing the oxidative degradation of L-tryptophan that contributes to immune suppression and tolerance
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
-
the initial deprotonation reaction of the indole NH group in hTDO is carried out by the evolutionarily conserved distal His. stereospecificity of hTDO is determined by the efficiency of the dioxygen chemistry
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
IDO displays a similar kcat for D- and L-tryptophan, but D-tryptophan has 173folds higher Km
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
-
L-Trp is a better substrate for IDO than D-Trp
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
-
human TDO displays a major specificity towards L-Trp, structural role of T342 in controlling the substrate stereoselectivity of the enzyme
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
-
highly preferred substrate, T342 plays a pivotal role in controlling the substrate stereoselectivity of hTDO
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
the enzyme has broad substrate specificity for various indoleamines such as L-tryptophan and serotonin. It catalyzes the oxidation of the pyrrole ring of tryptophan to form N-formylkynurenine, which is later metabolized to formic acid and kynurenine
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
the reaction involves cleavage of the C2=C3 double bond in the Trp indole ring and insertion of two atomic oxygens from the iron-bound O2 into the indole 2 and 3 position
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
-
no activity with oxygen concentrations below 0.1 mM, maximum activity at 1.15 mM oxygen
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
-
first step during biosynthesis of 3-hydroxyquinaldic acid
-
-
ir
L-tryptophan + O2
N-formyl-L-kynurenine
-
-
663820, 663910, 665204, 665457, 666461, 666895, 684391, 686721, 687116, 710831, 711165, 712112, 712152, 712821, 713412, 713448, 713586
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
-
IDO represents an important immune regulatory enzyme under diverse physiological and pathological conditions in vivo and is of considerable medical importance
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
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indoleamine 2,3-dioxygenase is a rate-limiting enzyme in the L-tryptophan-kynurenine pathway. IFN-gamma-induced expression of IDO expression is inhibited only by JAK inhibitor I. Lipopolysaccharide-induced expression of indoleamine 2,3-dioxygenase is inhibited by LY294002 and SP600125 but not by JAK inhibitor I, SB203580, or U0126. LPS can induce the expression of indoleamine 2,3-dioxygenase via an IFN-gamma-independent mechanism and PI3 kinase and JNK in the LPS-induced pathway leading to IDO expression
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L-tryptophan + O2
N-formyl-L-kynurenine
the enzyme has broad substrate specificity for various indoleamines such as L-tryptophan and serotonin. It catalyzes the oxidation of the pyrrole ring of tryptophan to form N-formylkynurenine, which is later metabolized to formic acid and kynurenine
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L-tryptophan + O2
N-formyl-L-kynurenine
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L-tryptophan + O2
N-formyl-L-kynurenine
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higher affinity at alkaline pH than at acidic pH
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L-tryptophan + O2
N-formyl-L-kynurenine
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the enzyme is involved in the catabolic pathway of L-tryptophan degradation, overview
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L-tryptophan + O2
N-formyl-L-kynurenine
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D-tryptophan is no substrate
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L-tryptophan + O2
N-formyl-L-kynurenine
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no activity with oxygen concentrations below 0.1 mM, maximum activity at 1.15 mM oxygen
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L-tryptophan + O2
N-formyl-L-kynurenine
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rate-limiting enzyme in L-tryptophan catabolism and thus a key serotonergic determinant
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L-tryptophan + O2
N-formyl-L-kynurenine
while L and D-tryptophan have similar affinities (Km values), the kcat is 10times lower for D-tryptophan
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L-tryptophan + O2
N-formylkynurenine
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additional information
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first and rate-limiting enzyme in tryptophan metabolism
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first enzyme of the kynurenine pathway of tryptophan metabolism
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in the placenta, inhibition of the enzyme leads to spontaneous abortion. By catabolizing extracellular tryptophan the enzyme inhibits local T cell proliferation thereby preventing placental rejection. This mechanism can also be active in suppressing inflammatory responses in the central neurvous system, where inflammation must be tightly regulated to prevent the loss of irreplaceable neurons. Local expression of the enzyme during inflammation is a self-protection mechanism which limits antigen-specific immune responses in the central nervous system
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Langerhans cells possess an immunoregulatory function in promoting T cell tolerance by production of IDO
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the oxidative metabolism of melatonin is due, in presence of H2O2, to the activities of both myeloperoxidase, EC 1.11.1.7 and indolemanine 2,3-dioxygenase
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the enzyme plays an important physiological role in the defense mechanism against a variety of infectious pathogens, in the regulation of T-cell function by macrophages and a subset of dendritic cells, and in the synthesis of UV filters in human lenses. Serious problems arise from the unregulated over-expression of the enzyme, which often results in a deleterious systemic Trp depletion and/or the accumulation of neurotoxin, quinolinic acidn the brain. Enzyme expression in malignant tumors helps them to avoid the immune surveillance through a local Trp depletion. The kynurenilation of the lens protein with UV filters thus appears to be the major cause of age-related cataract
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the IDO enzyme is involved in the immune regulation of early atherosclerosis, particularly in young female adults
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docking calculations and spatial coarse graining simulations are used to determine the molecular basis of substrate recognition, enhancer binding and conformational transitions of IDO in response to these events
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no activity with tryptophanol, indole-3-propionic acid, tryptamine, N-methyl-Trp
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no activity with tryptophanol, indole-3-propionic acid, tryptamine, N-methyl-Trp
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the enzyme acts as a heme peroxidase that, in the absence of substrates, self-inactivates dioxygenase activity via compound I-initiated protein oxidation. L-Trp protects against dioxygenase inactivation by reacting with compound I and retarding compound II reduction to suppress peroxidase turnover. Catalytic cycle of hemeperoxidase enzymes, and enzyme peroxidase mechanism, overview
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the enzyme catalyzes the oxidation of indole by H2O2, with generation of 2- and 3-oxoindole as the major products, in the absence of O2 and reducing agents and is not inhibited by superoxide dismutase or hydroxyl radical scavengers, although it is strongly inhibited by L-Trp. IDO inserts oxygen into indole in a reaction that is mechanistically analogous to the peroxide shunt pathway of cytochrome P450
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formation of ferrous-oxy hIDO and comparison with the ternary complex, overview
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substrate specificity, overview. Replacement of the 5-methoxy group by a methyl group has a negative influence in the binding of the molecule, decreasing its affinity threefold. 5-HO-L-Trp and melatonin are no substrates for IDO2
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additional information
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substrate specificity, overview. Replacement of the 5-methoxy group by a methyl group has a negative influence in the binding of the molecule, decreasing its affinity threefold. 5-HO-L-Trp and melatonin are no substrates for IDO2
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additional information
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substrate specificity, overview. Replacement of the 5-methoxy group by a methyl group has a negative influence in the binding of the molecule, decreasing its affinity threefold. 5-HO-L-Trp and melatonin are no substrates for IDO2
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the heme enzyme catalyzes the oxidative cleavage of the Ltryptophan indole ring
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the heme enzyme catalyzes the oxidative cleavage of the Ltryptophan indole ring
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using a cytochrome b5-based activating system, the initial rates of O2 decay with a Clark-type oxygen electrode at physiologically-relevant levels of both substrates are measured. Kinetics are also studied in the presence of two inhibitory substrate analogues: 1-methyl L-tryptophan and norharmane. Quantitative analysis supports a steady-state rather than a rapid equilibrium kinetic mechanism, where the rates of individual pathways, leading to a ternary complex, are significantly different, and the overall rate of catalysis depends on contributions of both routes. One path, where O2 binds to ferrous hIDO1 first, is faster than the second route, which starts with the binding of L-Trp. L-Trp complexation with free ferrous hIDO1 is more rapid than that of O2. As the level of L-Trp increases, the slower route becomes a significant contributor to the overall rate, resulting in observed substrate inhibition. When 1-Me-L-Trp is the only indoleamine in the reaction mixture, it is a very slow substrate for hIDO1
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additional information
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using a cytochrome b5-based activating system, the initial rates of O2 decay with a Clark-type oxygen electrode at physiologically-relevant levels of both substrates are measured. Kinetics are also studied in the presence of two inhibitory substrate analogues: 1-methyl L-tryptophan and norharmane. Quantitative analysis supports a steady-state rather than a rapid equilibrium kinetic mechanism, where the rates of individual pathways, leading to a ternary complex, are significantly different, and the overall rate of catalysis depends on contributions of both routes. One path, where O2 binds to ferrous hIDO1 first, is faster than the second route, which starts with the binding of L-Trp. L-Trp complexation with free ferrous hIDO1 is more rapid than that of O2. As the level of L-Trp increases, the slower route becomes a significant contributor to the overall rate, resulting in observed substrate inhibition. When 1-Me-L-Trp is the only indoleamine in the reaction mixture, it is a very slow substrate for hIDO1
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TioF is completely inactive towards tryptamine, 5-hydroxy-L-Trp, and indole propionic acid
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TioF is completely inactive towards tryptamine, 5-hydroxy-L-Trp, and indole propionic acid
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IDO2 enzyme may be involved in immune evasion by tumours
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IDO2 enzyme may be involved in immune evasion by tumours
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Trp suppresses 2,3-dioxygenase induction by IFN-gamma at the transcriptional level
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Trp suppresses 2,3-dioxygenase induction by IFN-gamma at the transcriptional level
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although the kcat of indoleamine-2,3-dioxygenase (IDO) is similar for D-Trp and L-Trp, the Km of IDO is approximately 170fold higher for L-Trp than that for D-Trp
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additional information
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although the kcat of indoleamine-2,3-dioxygenase (IDO) is similar for D-Trp and L-Trp, the Km of IDO is approximately 170fold higher for L-Trp than that for D-Trp
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in the presence of guaiacol or potassium iodide the enzyme degrades H2O2
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not active with indoleacetic acid and skatole
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no activity with D-Trp and indolepropionic acid
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no activity with D-Trp and indolepropionic acid
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no activity with D-Trp
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additional information
additional information
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no activity with D-Trp
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