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Information on EC 1.13.11.11 - tryptophan 2,3-dioxygenase
for references in articles please use BRENDA:EC1.13.11.11
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EC Tree 1 Oxidoreductases
1.13 Acting on single donors with incorporation of molecular oxygen (oxygenases)
1.13.11 With incorporation of two atoms of oxygen
1.13.11.11 tryptophan 2,3-dioxygenase
IUBMB Comments
A protohemoprotein. In mammals, the enzyme appears to be located only in the liver. This enzyme, together with EC 1.13.11.52, indoleamine 2,3-dioxygenase, catalyses the first and rate-limiting step in the kynurenine pathway, the major pathway of tryptophan metabolism . The enzyme is specific for tryptophan as substrate, but is far more active with L-tryptophan than with D-tryptophan .
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
- 1.13.11.11
- indoleamine
- kynurenine
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immunotherapy
- heme
- serotonin
-
checkpoint
- l-trp
- n-formylkynurenine
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quinolinic
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tolerogenic
-
3-monooxygenase
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3,4-dioxygenase
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heme-containing
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2,3-dioxygenase-1
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tryptophan-degrading
- 3-hydroxyanthranilate
- indoleamine-2,3-dioxygenase
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picolinic
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tryptophan-catabolizing
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pyrrolase
- 3-hydroxykynurenine
- medicine
- drug development
showSynonyms
tryptophan 2,3-dioxygenase, indoleamine 2,3-dioxygenase 1, ido-1, tryptophan-2,3-dioxygenase, indoleamine 2,3-dioxygenase 2, ido-2, tryptophan 2,3-dioxygenase 2, xctdo, l-tryptophan:oxygen 2,3-oxidoreductase (decyclizing), more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
EC 1.11.1.4
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-
formerly
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IDO-1
TDO
TDO2
tryptophan 2,3-dioxygenase 2
XcTDO
TDO
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-tryptophan + O2 = N-formyl-L-kynurenine
the dioxygenation reaction is initiated by a direct attack of O2 on the C2 atom of the L-Trp indole ring, catalytic mechanism, overview. Exo binding site for L-Trp, located about 42 A from the active site and formed by residues conserved among tryptophan-auxotrophic TDOs. Trp binding at this exo site does not affect enzyme catalysis but instead it retards the degradation of hTDO through the ubiquitin-dependent proteasomal pathway
L-tryptophan + O2 = N-formyl-L-kynurenine
catalytic mechanism, modeling. hTDO exists as two discrete species with markedly different ligand binding properties. The active site environment of the slowly rebinding species is structurally very heterogeneous and ligand access to greatly hindered. Binding of the L-Trp substrate stabilizes the faster-binding species, which features a well-structured active site and offers facile access of the ligand to the heme iron. This mechanism ensures that the ternary complex forms mainly by first binding the L-Trp substrate, which primes the active site for the subsequent binding of O2, which ensures efficient enzyme action
L-tryptophan + O2 = N-formyl-L-kynurenine
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PATHWAY SOURCE
PATHWAYS
BRENDA
MetaCyc
3-hydroxy-4-methyl-anthranilate biosynthesis I, 3-hydroxy-4-methyl-anthranilate biosynthesis II, L-tryptophan degradation I (via anthranilate), L-tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde, L-tryptophan degradation XI (mammalian, via kynurenine)
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SYSTEMATIC NAME
IUBMB Comments
L-tryptophan:oxygen 2,3-oxidoreductase (decyclizing)
A protohemoprotein. In mammals, the enzyme appears to be located only in the liver. This enzyme, together with EC 1.13.11.52, indoleamine 2,3-dioxygenase, catalyses the first and rate-limiting step in the kynurenine pathway, the major pathway of tryptophan metabolism [5]. The enzyme is specific for tryptophan as substrate, but is far more active with L-tryptophan than with D-tryptophan [2].
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-tryptophan + O2
3alpha-hydroxyhexahydropyrrolo[2,3-b]indole-2-carboxylic acid
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5-fluoro-L-tryptophan + O2
5-fluoro-N-formyl-L-kynurenine
Substrates: -
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5-fluoro-L-tryptophan + O2
5-fluoro-N-formyl-L-kynurenine
Substrates: -
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5-fluoro-L-tryptophan + O2
5-fluoro-N-formyl-L-kynurenine
Substrates: -
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D-tryptophan + O2
N-formyl-D-kynurenine
Substrates: low activity
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D-tryptophan + O2
N-formyl-D-kynurenine
Substrates: low activity
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indole-3-pyruvic acid + O2
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indole-3-pyruvic acid + O2
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L-tryptophan + O2
N-formyl-L-kynurenine
Substrates: -
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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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L-tryptophan + O2
N-formyl-L-kynurenine
Substrates: kinetic and spectroscopic characterization of the catalytic ternary complex of tryptophan 2,3-dioxygenase
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L-tryptophan + O2
N-formyl-L-kynurenine
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L-tryptophan + O2
N-formyl-L-kynurenine
Substrates: kinetic and spectroscopic characterization of the catalytic ternary complex of tryptophan 2,3-dioxygenase
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L-tryptophan + O2
N-formyl-L-kynurenine
Substrates: -
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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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L-tryptophan + O2
N-formyl-L-kynurenine
Substrates: cleavage of the C2-C3 bond in the indole moiety of L-Trp and incorporation of one oxygen molecule
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L-tryptophan + O2
N-formyl-L-kynurenine
Substrates: 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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L-tryptophan + O2
N-formyl-L-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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L-tryptophan + O2
N-formyl-L-kynurenine
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L-tryptophan + O2
N-formyl-L-kynurenine
Substrates: 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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L-tryptophan + O2
N-formyl-L-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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L-tryptophan + O2
N-formyl-L-kynurenine
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L-tryptophan + O2
N-formyl-L-kynurenine
Substrates: -
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additional information
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Substrates: enzyme TDO is highly substrate-specific for L-Trp and the related derivatives 6-fluoro-Trp and 5-fluoro-Trp
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Substrates: enzyme TDO is highly substrate-specific for L-Trp and the related derivatives 6-fluoro-Trp and 5-fluoro-Trp
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additional information
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Substrates: substrate recognition and binding structures, overview. The EG segment in hTDO plays a critical role in promoting NFK release, thereby allowing Trp binding during multiple turnover
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additional information
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Substrates: substrate recognition and binding structures, overview. The EG segment in hTDO plays a critical role in promoting NFK release, thereby allowing Trp binding during multiple turnover
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additional information
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Substrates: no activity with D-Trp. No evidence for the accumulation of Compound II during TDO catalysis, instead a ternary [Fe(II)-O2, L-Trp] complex is detected under steady state conditions. Absence of a Compound II species in the steady state in TDO is not due to an intrinsic inability of the TDO enzyme to form ferryl heme, because Compound II can be formed directly through a different route in which ferrous heme is reacted with peroxide
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Substrates: enzyme-CO binding analysis, overview
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Substrates: enzyme-CO binding analysis, overview
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Substrates: in mouse liver homogenate, TDO activity is five times lower for D-Trp than that for L-Trp. L-Trp is the preferred substrate for nicotinamide synthesis because L-Trp metabolism is more efficient than D-Trp in mice
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Substrates: the kcat of tryptophan-2,3-dioxygenase (TDO) is 10 times lower for D-Trp than that for L-Trp in vitro
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additional information
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Substrates: in mouse liver homogenate, TDO activity is five times lower for D-Trp than that for L-Trp. L-Trp is the preferred substrate for nicotinamide synthesis because L-Trp metabolism is more efficient than D-Trp in mice
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Substrates: the kcat of tryptophan-2,3-dioxygenase (TDO) is 10 times lower for D-Trp than that for L-Trp in vitro
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additional information
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Substrates: no activity witth D-Trp. No evidence for the accumulation of Compound II during TDO catalysis, instead a ternary [Fe(II)-O2, L-Trp] complex is detected under steady state conditions. Absence of a Compound II species in the steady state in TDO is not due to an intrinsic inability of the TDO enzyme to form ferryl heme, because Compound II can be formed directly through a different route in which ferrous heme is reacted with peroxide
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additional information
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Substrates: no activity witth D-Trp. No evidence for the accumulation of Compound II during TDO catalysis, instead a ternary [Fe(II)-O2, L-Trp] complex is detected under steady state conditions. Absence of a Compound II species in the steady state in TDO is not due to an intrinsic inability of the TDO enzyme to form ferryl heme, because Compound II can be formed directly through a different route in which ferrous heme is reacted with peroxide
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
D-tryptophan + O2
N-formyl-D-kynurenine
Substrates: low activity
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D-tryptophan + O2
N-formyl-D-kynurenine
Substrates: low activity
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L-tryptophan + O2
N-formyl-L-kynurenine
Substrates: -
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L-tryptophan + O2
N-formyl-L-kynurenine
Substrates: -
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L-tryptophan + O2
N-formyl-L-kynurenine
Substrates: -
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L-tryptophan + O2
N-formyl-L-kynurenine
Substrates: -
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L-tryptophan + O2
N-formyl-L-kynurenine
Substrates: -
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L-tryptophan + O2
N-formyl-L-kynurenine
Substrates: -
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L-tryptophan + O2
N-formyl-L-kynurenine
Substrates: -
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L-tryptophan + O2
N-formyl-L-kynurenine
Substrates: -
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L-tryptophan + O2
N-formyl-L-kynurenine
Substrates: -
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L-tryptophan + O2
N-formyl-L-kynurenine
Substrates: -
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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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L-tryptophan + O2
N-formyl-L-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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L-tryptophan + O2
N-formyl-L-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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L-tryptophan + O2
N-formyl-L-kynurenine
Substrates: -
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L-tryptophan + O2
N-formyl-L-kynurenine
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additional information
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Substrates: in mouse liver homogenate, TDO activity is five times lower for D-Trp than that for L-Trp. L-Trp is the preferred substrate for nicotinamide synthesis because L-Trp metabolism is more efficient than D-Trp in mice
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additional information
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Substrates: in mouse liver homogenate, TDO activity is five times lower for D-Trp than that for L-Trp. L-Trp is the preferred substrate for nicotinamide synthesis because L-Trp metabolism is more efficient than D-Trp in mice
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
heme
heme-containing enzyme. The heme prosthetic group is present as a heme-ferric form that must be reduced to the heme-ferrous prior to mediate L-tryptophan oxidation
heme
the enzyme is heme dependent, requiring the reduction of ferric to ferrous-iron to bind to L-tryptophan
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1R,2S)-2-([[6-(trifluoromethyl)-1H-indazol-4-yl]amino]methyl)cyclohexan-1-ol
-
(1R,2S)-2-[[(6-bromo-1-methyl-1H-indazol-4-yl)amino]methyl]cyclohexan-1-ol
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(2E)-3-(8-fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazolin-2-yl)prop-2-enoic acid
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(8-fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazolin-2-yl)boronic acid
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1-(2-hydroxy-4-methylphenyl)-3-{2-[(propan-2-yl)oxy]phenyl}propane-1,3-dione
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1-(3-bromothiophen-2-yl)-2-(3-methyl-1,4-dihydronaphthalen-2-yl)ethan-1-one
most potent inhibitor capable of blocking both indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2) activity, with the IC50 value for BT-549 cells at 0.00342 mM
1-(3-[(4-acetyl-1-piperazinyl)carbonyl]benzyl)-1H-naphtho-[2,3-d][1,2,3]triazole-4,9-dione
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1-(3-[(4-methyl-1-piperazinyl)carbonyl]benzyl)-1H-naphtho-[2,3-d][1,2,3]triazole-4,9-dione
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1-(4-[(4-acetylpiperazin-1-yl)carbonyl]benzyl)-1H-naphtho-[2,3-d][1,2,3]triazole-4,9-dione
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1-(4-[(4-methoxypiperidin-1-yl)carbonyl]benzyl)-1Hnaphtho[2,3-d][1,2,3]triazole-4,9-dione
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1-[(8-fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazolin-2-yl)methyl]piperidine-3-carboxylic acid
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1-[(8-fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazolin-2-yl)methyl]piperidine-4-carboxylic acid
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1-[(8-fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazolin-2-yl)methyl]proline
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1-[3-(4-morpholinylcarbonyl)benzyl]-1H-naphtho[2,3-d]-[1,2,3]triazole-4,9-dione
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1-[4-(morpholin-4-ylcarbonyl)benzyl]-1H-naphtho[2,3-d]-[1,2,3]triazole-4,9-dione
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1-[4-[(4-methylpiperazin-1-yl)carbonyl]benzyl]-1H-naphtho-[2,3-d][1,2,3]triazole-4,9-dione
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2-(4-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]-triazol-1-yl)methyl]phenyl)-N,N-diethylacetamide
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3-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)methyl]-N,N-diethylbenzamide
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3-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)methyl]benzoic acid
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4-([[(1S,2R)-2-hydroxycyclohexyl]methyl]amino)-1H-indazole-6-carboxylic acid
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4-[(1Z)-2-[(6-bromo-1H-indazol-4-yl)amino]-N-hydroxyethanimidoyl]phenol
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4-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)methyl]-N,N-diethylbenzamide
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4-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)methyl]benzoic acid
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5-(6-fluoro-1H-indol-3-yl)-1-[2-(piperazin-1-yl)ethyl]-1H-benzotriazole
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5-phenyl-1,2,3-thiadiazol-4-amine
potent tryptophan 2,3-dioxygenase 2 inhibitor with modest selectivity over indolamine 2,3-dioxygenase 1 and with improved human whole blood stability
8-fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indolo[2,1-b]quinazoline-6,12-dione
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8-fluoro-2-[(1H-1,2,3-triazol-1-yl)methyl]indolo[2,1-b]quinazoline-6,12-dione
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8-fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazoline-2-carbaldehyde
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ethyl (2E)-3-(8-fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazolin-2-yl)prop-2-enoate
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methyl 1-[(8-fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazolin-2-yl)methyl]piperidine-3-carboxylate
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methyl 1-[(8-fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazolin-2-yl)methyl]piperidine-4-carboxylate
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methyl 1-[(8-fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazolin-2-yl)methyl]prolinate
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methyl 4-([[(1S,2R)-2-hydroxycyclohexyl]methyl]amino)-1H-indazole-6-carboxylate
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N-(3-bromo-4-fluorophenyl)-N'-hydroxy-4-[[2-(sulfamoylamino)ethyl]amino]-1,2,5-oxadiazole-3-carboximidamide
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N-(4-[[(6-bromo-1H-indazol-4-yl)amino]methyl]cyclohexylidene)hydroxylamine
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tert-butyl 3-[[(6-bromo-1H-indazol-4-yl)amino]methyl]pyrrolidine-1-carboxylate
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additional information
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isatin derivatives analysis as a class of TDO inhibitors, structure-activity relationships and molecular docking studies, and optimized the inhibition potency of isatin derivatives by over 130fold, overview. Hydrogen bond interactions between the compound and key active site residues of TDO, freedom upon rotation of the C3 chemical moiety and the presence of chlorines in the benzene ring of the compound comprise the properties that an isatin-based inhibitor requires to effectively inhibit the enzymatic activity of enzyme TDO
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additional information
identification of substituted naphthotriazolediones as tryptophan 2,3-dioxygenase (TDO) inhibitors through structure-based virtual screening, homology modeling and virtual screening, ligand docking analysis, overview
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additional information
the enzymatic and cellular assays are influenced by many factors including detection product, reaction time and culture medium, which may cause the inconsistency of enzymatic and cellular inhibitory activities of test compounds. The TDO IC50 values of all the test compounds derived from NFK assay are 2-3 times higher than that of Kyn adduct assay
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additional information
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the enzymatic and cellular assays are influenced by many factors including detection product, reaction time and culture medium, which may cause the inconsistency of enzymatic and cellular inhibitory activities of test compounds. The TDO IC50 values of all the test compounds derived from NFK assay are 2-3 times higher than that of Kyn adduct assay
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additional information
1H-indazole-4-amines inhibit both human indoleamine 2,3-dioxygenase 1 (hIDO1) and tryptophan 2,3-dioxygenase (hTDO) by a mechanism involving direct coordination with the heme ferrous and ferric states
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additional information
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1H-indazole-4-amines inhibit both human indoleamine 2,3-dioxygenase 1 (hIDO1) and tryptophan 2,3-dioxygenase (hTDO) by a mechanism involving direct coordination with the heme ferrous and ferric states
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
H2O2
activation of the enzyme is stimulated by superoxide and H2O2
superoxide
activation of the enzyme is stimulated by superoxide and H2O2
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.02
L-tryptophan
pH and temperature not specified in the publication
0.19
L-tryptophan
pH and temperature not specified in the publication
additional information
additional information
Michaelis-Menten kinetics
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additional information
additional information
stopped-flow, pre-steady-state, and steady-state kinetics
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additional information
additional information
stopped-flow, pre-steady-state, and steady-state kinetics
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additional information
additional information
reaction and ligand binding kinetics, two hTDO conformations exist that bind CO in a bimolecular reaction, but with very different rates, kinetic calculations, overview
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additional information
additional information
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reaction and ligand binding kinetics, two hTDO conformations exist that bind CO in a bimolecular reaction, but with very different rates, kinetic calculations, overview
-
additional information
additional information
Michaelis-Menten kinetics
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additional information
additional information
Michaelis-Menten kinetics
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additional information
additional information
Michaelis-Menten kinetics
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additional information
additional information
Michaelis-Menten kinetics
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additional information
additional information
Michaelis-Menten kinetics
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additional information
additional information
Michaelis-Menten kinetics
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additional information
additional information
Michaelis-Menten kinetics
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additional information
additional information
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Michaelis-Menten kinetics
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0004
(1R,2S)-2-([[6-(trifluoromethyl)-1H-indazol-4-yl]amino]methyl)cyclohexan-1-ol
Homo sapiens
22°C, pH 6.5
0.01124
(1R,2S)-2-[[(5-bromo-1H-indazol-4-yl)amino]methyl]cyclohexan-1-ol
Homo sapiens
22°C, pH 6.5
0.03916
(1R,2S)-2-[[(5-bromo-1H-indazol-7-yl)amino]methyl]cyclohexan-1-ol
Homo sapiens
22°C, pH 6.5
0.08419
(1R,2S)-2-[[(5-chloro-1H-indazol-7-yl)amino]methyl]cyclohexan-1-ol
Homo sapiens
22°C, pH 6.5
0.03324
(1R,2S)-2-[[(6-bromo-1-methyl-1H-indazol-4-yl)amino]methyl]cyclohexan-1-ol
Homo sapiens
22°C, pH 6.5
0.00004
(1R,2S)-2-[[(6-bromo-1H-indazol-4-yl)amino]methyl]cyclohexan-1-ol
Homo sapiens
shows efficacy against the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse motor coordination deficits, comparable to Madopar, an anti-Parkinson's disease medicine, 22°C, pH 6.5
0.00019
(1R,2S)-2-[[(6-bromo-1H-indazol-4-yl)amino]methyl]cyclohexyl acetate
Homo sapiens
22°C, pH 6.5
0.00013
(1R,2S)-2-[[(6-chloro-1H-indazol-4-yl)amino]methyl]cyclohexan-1-ol
Homo sapiens
22°C, pH 6.5
0.00041
(1R,2S)-2-[[(6-methyl-1H-indazol-4-yl)amino]methyl]cyclohexan-1-ol
Homo sapiens
22°C, pH 6.5
0.00009
(1S,2R)-2-[[(6-bromo-1H-indazol-4-yl)amino]methyl]cyclohexan-1-ol
Homo sapiens
22°C, pH 6.5
0.00003
(2E)-3-(8-fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazolin-2-yl)prop-2-enoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0044
(4-phenyl-1,2-oxazol-5-yl)methanol
Homo sapiens
pH and temperature not specified in the publication
0.00121
(8-fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazolin-2-yl)boronic acid
Homo sapiens
pH and temperature not specified in the publication
0.000561
1-(2-methylbenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
Homo sapiens
pH 8.0, 37°C
0.000768
1-(3-bromobenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
Homo sapiens
pH 8.0, 37°C
0.000711
1-(3-chlorobenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
Homo sapiens
pH 8.0, 37°C
0.000059
1-(3-[(4-acetyl-1-piperazinyl)carbonyl]benzyl)-1H-naphtho-[2,3-d][1,2,3]triazole-4,9-dione
Homo sapiens
pH 8.0, 37°C
0.00003
1-(3-[(4-methyl-1-piperazinyl)carbonyl]benzyl)-1H-naphtho-[2,3-d][1,2,3]triazole-4,9-dione
Homo sapiens
pH 8.0, 37°C
0.001586
1-(4-bromobenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
Homo sapiens
pH 8.0, 37°C
0.00738
1-(4-fluorobenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
Homo sapiens
pH 8.0, 37°C
0.001088
1-(4-methylbenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
Homo sapiens
pH 8.0, 37°C
0.000176
1-(4-[(4-acetylpiperazin-1-yl)carbonyl]benzyl)-1H-naphtho-[2,3-d][1,2,3]triazole-4,9-dione
Homo sapiens
pH 8.0, 37°C
0.000209
1-(4-[(4-methoxypiperidin-1-yl)carbonyl]benzyl)-1Hnaphtho[2,3-d][1,2,3]triazole-4,9-dione
Homo sapiens
pH 8.0, 37°C
0.0135
1-(cyclopropylmethyl)-5-(1H-indol-3-yl)-1H-benzotriazole
Homo sapiens
37°C, pH 6.25
0.0039
1-(cyclopropylmethyl)-6-(1H-indol-3-yl)-1H-benzotriazole
Homo sapiens
37°C, pH 6.26
0.00015
1-cyclohexyl-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethan-1-ol
Homo sapiens
22°C, pH 6.5
0.001745
1-[(3-methylphenyl)methyl]-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
Homo sapiens
pH 8.0, 37°C
0.00646
1-[(4-chlorophenyl)methyl]-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
Homo sapiens
pH 8.0, 37°C
0.00042
1-[(8-fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazolin-2-yl)methyl]piperidine-3-carboxylic acid
Homo sapiens
pH and temperature not specified in the publication
0.00045
1-[(8-fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazolin-2-yl)methyl]piperidine-4-carboxylic acid
Homo sapiens
pH and temperature not specified in the publication
0.00018
1-[(8-fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazolin-2-yl)methyl]proline
Homo sapiens
pH and temperature not specified in the publication
0.000048
1-[3-(4-morpholinylcarbonyl)benzyl]-1H-naphtho[2,3-d]-[1,2,3]triazole-4,9-dione
Homo sapiens
pH 8.0, 37°C
0.000116
1-[4-(morpholin-4-ylcarbonyl)benzyl]-1H-naphtho[2,3-d]-[1,2,3]triazole-4,9-dione
Homo sapiens
pH 8.0, 37°C
0.000108
1-[4-[(4-methylpiperazin-1-yl)carbonyl]benzyl]-1H-naphtho-[2,3-d][1,2,3]triazole-4,9-dione
Homo sapiens
pH 8.0, 37°C
0.000145
2-(4-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]-triazol-1-yl)methyl]phenyl)-N,N-diethylacetamide
Homo sapiens
pH 8.0, 37°C
0.00338
2-[(6-bromo-1H-indazol-4-yl)amino]-1-(3-chlorophenyl)ethan-1-ol
Homo sapiens
22°C, pH 6.5
0.1477
2-[(6-bromo-1H-indazol-4-yl)amino]-1-(4-hydroxyphenyl)ethan-1-one
Homo sapiens
22°C, pH 6.5
0.00204
2-[(6-bromo-1H-indazol-4-yl)amino]-2-(3-chlorophenyl)ethan-1-ol
Homo sapiens
22°C, pH 6.5
0.00033
2-[(6-bromo-1H-indazol-4-yl)amino]-2-phenylethan-1-ol
Homo sapiens
22°C, pH 6.5
0.0369
2-[5-(1H-indol-3-yl)-1H-benzotriazol-1-yl]-N,N-dimethylethan-1-amine
Homo sapiens
37°C, pH 6.31
0.00162
2-[5-(1H-indol-3-yl)-1H-benzotriazol-1-yl]acetamide
Homo sapiens
37°C, pH 6.27
0.0246
2-[6-(1H-indol-3-yl)-1H-benzotriazol-1-yl]-N,N-dimethylethan-1-amine
Homo sapiens
37°C, pH 6.32
0.00068
2-[6-(1H-indol-3-yl)-1H-benzotriazol-1-yl]acetamide
Homo sapiens
37°C, pH 6.28
0.00012
2-[[(6-bromo-1H-indazol-4-yl)amino]methyl]cyclohexan-1-ol
Homo sapiens
22°C, pH 6.5
0.025
3-methyl-4-phenyl-1,2-oxazol-5-amine
Homo sapiens
pH and temperature not specified in the publication
0.00009
3-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)methyl]-N,N-diethylbenzamide
Homo sapiens
pH 8.0, 37°C
0.000167
3-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)methyl]benzoic acid
Homo sapiens
pH 8.0, 37°C
0.017
3-[5-(1H-indol-3-yl)-1H-benzotriazol-1-yl]propane-1,2-diol
Homo sapiens
37°C, pH 6.46
0.0252
3-[6-(1H-indol-3-yl)-1H-benzotriazol-1-yl]propane-1,2-diol
Homo sapiens
37°C, pH 6.47
0.00029
4-(1H-pyrazol-1-yl)-1,2-oxazol-5-amine
Homo sapiens
pH and temperature not specified in the publication
0.0005
4-(3-chlorophenyl)-1,2-oxazol-5-amine
Homo sapiens
pH and temperature not specified in the publication
0.00033
4-(3-chlorophenyl)-imidazole
Homo sapiens
pH and temperature not specified in the publication
-
0.0031
4-(3-methoxyphenyl)-1,2-oxazol-5-amine
Homo sapiens
pH and temperature not specified in the publication
0.0016
4-(3-methyl-1H-pyrazol-1-yl)-1,2-oxazol-5-amine
Homo sapiens
pH and temperature not specified in the publication
0.00083
4-(4-chlorophenyl)-1,2-oxazol-5-amine
Homo sapiens
pH and temperature not specified in the publication
0.00034
4-(4-fluoro-1H-pyrazol-1-yl)-1,2-oxazol-5-amine
Homo sapiens
pH and temperature not specified in the publication
0.00058
4-(4-fluorophenyl)-1,2-oxazol-5-amine
Homo sapiens
pH and temperature not specified in the publication
0.0016
4-(4-methyl-1H-pyrazol-1-yl)-1,2-oxazol-5-amine
Homo sapiens
pH and temperature not specified in the publication
0.0017
4-(pyridin-2-yl)-1,2-oxazol-5-amine
Homo sapiens
pH and temperature not specified in the publication
0.0023
4-(pyridin-3-yl)-1,2-oxazol-5-amine
Homo sapiens
pH and temperature not specified in the publication
0.000029
4-(thiophen-2-yl)-1,2-oxazol-5-amine
Homo sapiens
pH and temperature not specified in the publication
0.000028
4-(thiophen-3-yl)-1,2-oxazol-5-amine
Homo sapiens
pH and temperature not specified in the publication
0.02702
4-([[(1S,2R)-2-hydroxycyclohexyl]methyl]amino)-1H-indazole-6-carboxylic acid
Homo sapiens
22°C, pH 6.5
0.00011
4-chlorophenyl-1,2,3-triazol-4-amine
Homo sapiens
pH and temperature not specified in the publication
-
0.0078
4-cyclohexyl-1,2-oxazol-5-amine
Homo sapiens
pH and temperature not specified in the publication
0.00064
4-cyclopentyl-1,2-oxazol-5-amine
Homo sapiens
pH and temperature not specified in the publication
0.00014
4-phenyl-1,2-oxazol-5-amine
Homo sapiens
pH and temperature not specified in the publication
0.018
4-phenyl-1,2-thiazol-5-amine
Homo sapiens
pH and temperature not specified in the publication
0.00048
4-phenylimidazole
Homo sapiens
pH and temperature not specified in the publication
0.01286
4-[(1Z)-2-[(6-bromo-1H-indazol-4-yl)amino]-N-hydroxyethanimidoyl]phenol
Homo sapiens
22°C, pH 6.5
0.000181
4-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)methyl]-N,N-diethylbenzamide
Homo sapiens
pH 8.0, 37°C
0.000312
4-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)methyl]benzoic acid
Homo sapiens
pH 8.0, 37°C
0.015
5-(1H-indol-3-yl)-1-(2,2,2-trifluoroethyl)-1H-benzotriazole
Homo sapiens
37°C, pH 6.23
-
0.0369
5-(1H-indol-3-yl)-1-[(oxolan-2-yl)methyl]-1H-benzotriazole
Homo sapiens
37°C, pH 6.35
0.0441
5-(1H-indol-3-yl)-1-[(oxolan-3-yl)methyl]-1H-benzotriazole
Homo sapiens
37°C, pH 6.33
0.01773
5-(1H-indol-3-yl)-1-[(piperidin-4-yl)methyl]-1H-benzotriazole
Homo sapiens
37°C, pH 6.39
0.1186
5-(1H-indol-3-yl)-1-[2-(morpholin-4-yl)ethyl]-1H-benzotriazole
Homo sapiens
37°C, pH 6.37
0.0249
5-(1H-indol-3-yl)-1-[2-(piperazin-1-yl)ethyl]-1H-benzotriazole
Homo sapiens
37°C, pH 6.43
0.0261
5-(1H-indol-3-yl)-1-[2-(pyrrolidin-3-yl)ethyl]-1H-benzotriazole
Homo sapiens
37°C, pH 6.41
0.0011
5-(6-fluoro-1H-indol-3-yl)-1-methyl-1H-benzotriazole
Homo sapiens
37°C, pH 6.14
0.045
5-(6-fluoro-1H-indol-3-yl)-1-[2-(piperazin-1-yl)ethyl]-1H-benzotriazole
Homo sapiens
37°C, pH 6.44
0.0019
6-(1H-indol-3-yl)-1-(2,2,2-trifluoroethyl)-1H-benzotriazole
Homo sapiens
37°C, pH 6.24
0.00908
6-(1H-indol-3-yl)-1-methyl-1H-[1,2,3]triazolo[4,5-b]pyridine
Homo sapiens
37°C, pH 6.21
0.00132
6-(1H-indol-3-yl)-1-methyl-7-nitro-1H-benzotriazole
Homo sapiens
37°C, pH 6.22
0.0211
6-(1H-indol-3-yl)-1-[(oxolan-2-yl)methyl]-1H-benzotriazole
Homo sapiens
37°C, pH 6.36
0.0219
6-(1H-indol-3-yl)-1-[(oxolan-3-yl)methyl]-1H-benzotriazole
Homo sapiens
37°C, pH 6.34
0.02551
6-(1H-indol-3-yl)-1-[(piperidin-4-yl)methyl]-1H-benzotriazole
Homo sapiens
37°C, pH 6.40
0.04565
6-(1H-indol-3-yl)-1-[(pyrrolidin-3-yl)methyl]-1H-benzotriazole
Homo sapiens
37°C, pH 6.42
0.0526
6-(1H-indol-3-yl)-1-[2-(morpholin-4-yl)ethyl]-1H-benzotriazole
Homo sapiens
37°C, pH 6.38
0.0052
6-(1H-indol-3-yl)-1-[2-(piperazin-1-yl)ethyl]-1H-benzotriazole
Homo sapiens
37°C, pH 6.45
0.01306
6-(1H-indol-3-yl)-2-methyl-2H-[1,2,3]triazolo[4,5-b]pyridine
Homo sapiens
37°C, pH 6.19
0.00783
6-(1H-indol-3-yl)-3-methyl-3H-[1,2,3]triazolo[4,5-b]pyridine
Homo sapiens
37°C, pH 6.20
0.00204
6-bromo-N-[(1,4-dioxaspiro[4.5]decan-6-yl)methyl]-1H-indazol-4-amine
Homo sapiens
22°C, pH 6.5
0.05841
6-bromo-N-[(1R,2R)-2-hydroxycyclohexyl]-1H-indazole-4-carboxamide
Homo sapiens
22°C, pH 6.5
0.01044
6-bromo-N-[(pyrrolidin-3-yl)methyl]-1H-indazol-4-amine
Homo sapiens
22°C, pH 6.5
0.00022
6-bromo-N-[[(1S,2S)-2-chlorocyclohexyl]methyl]-1H-indazol-4-amine
Homo sapiens
22°C, pH 6.5
0.00185
6-bromo-N-[[(2R)-piperidin-2-yl]methyl]-1H-indazol-4-amine
Homo sapiens
22°C, pH 6.5
0.00745
6-bromo-N-[[(2R)-pyrrolidin-2-yl]methyl]-1H-indazol-4-amine
Homo sapiens
22°C, pH 6.5
0.00606
6-bromo-N-[[(2S)-piperidin-2-yl]methyl]-1H-indazol-4-amine
Homo sapiens
22°C, pH 6.5
0.00417
6-bromo-N-[[(2S)-pyrrolidin-2-yl]methyl]-1H-indazol-4-amine
Homo sapiens
22°C, pH 6.5
0.0061 - 0.0087
6-fluoro-3-[(E)-2-(1H-tetrazol-5-yl)ethenyl]-1H-indole
Homo sapiens
37°C, pH 6.5
0.0127 - 0.0229
7-(1H-indol-3-yl)-3,4-dihydroquinazolin-2(1H)-one
Homo sapiens
37°C, pH 6.10
0.00602
8-fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indolo[2,1-b]quinazoline-6,12-dione
Homo sapiens
pH and temperature not specified in the publication
0.00113
8-fluoro-2-[(1H-1,2,3-triazol-1-yl)methyl]indolo[2,1-b]quinazoline-6,12-dione
Homo sapiens
pH and temperature not specified in the publication
0.00006
8-fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazoline-2-carbaldehyde
Homo sapiens
pH and temperature not specified in the publication
0.00037
ethyl (2E)-3-(8-fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazolin-2-yl)prop-2-enoate
Homo sapiens
pH and temperature not specified in the publication
0.00287
methyl 1-[(8-fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazolin-2-yl)methyl]piperidine-3-carboxylate
Homo sapiens
pH and temperature not specified in the publication
0.00099
methyl 1-[(8-fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazolin-2-yl)methyl]piperidine-4-carboxylate
Homo sapiens
pH and temperature not specified in the publication
0.0003
methyl 1-[(8-fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazolin-2-yl)methyl]prolinate
Homo sapiens
pH and temperature not specified in the publication
0.01259
methyl 4-([[(1S,2R)-2-hydroxycyclohexyl]methyl]amino)-1H-indazole-6-carboxylate
Homo sapiens
22°C, pH 6.5
0.00777
N-(3-bromo-4-fluorophenyl)-N'-hydroxy-4-[[2-(sulfamoylamino)ethyl]amino]-1,2,5-oxadiazole-3-carboximidamide
Homo sapiens
22°C, pH 6.5
0.00045
N-(4-[[(6-bromo-1H-indazol-4-yl)amino]methyl]cyclohexylidene)hydroxylamine
Homo sapiens
22°C, pH 6.5
0.00019
N-methyl-4-phenyl-1,2-oxazol-5-amine
Homo sapiens
pH and temperature not specified in the publication
0.04487
N-[(azetidin-3-yl)methyl]-6-bromo-1H-indazol-4-amine
Homo sapiens
22°C, pH 6.5
0.00036
N-[[(1S,2R)-2-aminocyclohexyl]methyl]-6-bromo-1H-indazol-4-amine
Homo sapiens
22°C, pH 6.5
0.00091
N-[[(1S,2S)-2-aminocyclohexyl]methyl]-6-bromo-1H-indazol-4-amine
Homo sapiens
22°C, pH 6.5
0.00136
tert-butyl 3-[[(6-bromo-1H-indazol-4-yl)amino]methyl]pyrrolidine-1-carboxylate
Homo sapiens
22°C, pH 6.5
additional information
additional information
Homo sapiens
the enzymatic and cellular assays are influenced by many factors including detection product, reaction time and culture medium, which may cause the inconsistency of enzymatic and cellular inhibitory activities of test compounds. The IC50 values of all the test compounds derived from NFK assay are 2-3 times higher than that of Kyn adduct assay
-
additional information
additional information
Homo sapiens
-
the enzymatic and cellular assays are influenced by many factors including detection product, reaction time and culture medium, which may cause the inconsistency of enzymatic and cellular inhibitory activities of test compounds. The IC50 values of all the test compounds derived from NFK assay are 2-3 times higher than that of Kyn adduct assay
-
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
37
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
expression on brain occurs in different cells as macrophages, microglia, neurons and astrocytes
brenda
expression on brain occurs in different cells as macrophages, microglia, neurons and astrocytes
brenda
immune cells express high amount of the enzyme (TDO2) at the peak stage of adjuvant-induced arthritis
brenda
immune cells express high amount of the enzyme (TDO2) at the peak stage of adjuvant-induced arthritis
brenda
the enzyme is located in the oxygene-rich environment of the liver promoting greater amount of the enzyme in ferric form than in ferrous form, which could contribute to the binding to substrates occurs in this form
brenda
additional information
in human tumors IDO-2 is expressed, but it is produced in a functionally inactive form
brenda
additional information
in human tumors IDO-2 is expressed, but it is produced in a functionally inactive form
brenda
additional information
in human tumors IDO-2 is expressed, but it is produced in a functionally inactive form
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug target
evolution
malfunction
metabolism
physiological function
additional information
drug target
Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are promising drug development targets due to their implications in pathologies such as cancer and neurodegenerative diseases. IDO1/TDO dual inhibitors and provides chemical molecules for potential development into drugs
drug target
conversion of tryptophan to N-formylkynurenine is the first and rate-limiting step of the tryptophan metabolic pathway (i.e., the kynurenine pathway). This conversion is catalyzed by three enzyme isoforms: indoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), and tryptophan-2,3-dioxygenase (TDO). As this pathway generates numerous metabolites that are involved in various pathological conditions, IDOs and TDO represent important targets for therapeutic intervention. Despite their poor sequence similarities, their active sites are highly conserved, and therefore allow the design of inhibitors with multiple activities that can target at least two isoforms
drug target
the enzyme (TDO2) catalyzes the conversion of tryptophan to the immunosuppressive metabolite kynurenine. TDO2 overexpression has been observed in a number of cancers. Therefore, TDO inhibition may be a useful therapeutic intervention for cancers
drug target
tryptophan 2,3-dioxygenase is a therapeutic target for Parkinson's disease
drug target
human indoleamine 2,3-dioxygenase 1 (hIDO1) and tryptophan 2,3-dioxygenase (hTDO) are closely linked to the pathogenesis of Parkinson's disease
evolution
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) are heme-containing enzymes that catalyze the O2-dependent oxidation of L-tryptophan (L-Trp) in biological systems following different reaction mechanisms, the rate-limiting step in the IDO and TDO mechanisms is not the same
evolution
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) are heme-containing enzymes that catalyze the O2-dependent oxidation of L-tryptophan (L-Trp) in biological systems following different reaction mechanisms, the rate-limiting step in the IDO and TDO mechanisms is not the same
evolution
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview
evolution
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview
evolution
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview
evolution
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview
evolution
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview
evolution
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview
evolution
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview
evolution
-
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) enzymes have independently evolved to catalyze the first step in the catabolism of tryptophan (L-Trp) through the kynurenine pathway. Enzyme TDO is found in almost all metazoan and many bacterial species, but not in fungi, distribution of IDO/TDO genes among invertebrates, overview
evolution
-
indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) and tryptophan 2,3-dioxygenase (TDO) are heme-containing enzymes that catalyze the O2-dependent oxidation of L-tryptophan (L-Trp) in biological systems following different reaction mechanisms, the rate-limiting step in the IDO and TDO mechanisms is not the same
-
malfunction
TDO knockout mice require a minimum of 0.06% dietary L-Trp, which value is about 2 mg/d/mouse
malfunction
pharmacological inhibition or knockdown of the enzyme (TDO2) in adjuvant-induced arthritis-fibroblast-like synoviocytes results in a reduced proliferation, secretion, migration and invasion
malfunction
alterations in the activity of tryptophan 2,3-dioxygenase cause imbalances in the levels of serotonin and other neuroactive metabolites which can contribute to motor, psychiatric, gastrointestinal, and other dysfunctions often seen in Parkinson's disease
malfunction
pharmacological inhibition or knockdown of the enzyme (TDO2) in adjuvant-induced arthritis-fibroblast-like synoviocytes results in a reduced proliferation, secretion, migration and invasion
malfunction
-
TDO knockout mice require a minimum of 0.06% dietary L-Trp, which value is about 2 mg/d/mouse
-
metabolism
comparison of contribution percentage of tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) to the conversion of L-tryptophan, the calculated percentage conversions indicats that TDO and IDO oxidize 70% and 30%, respectively, of the dietary L-tryptophan. The amount of D-Trp converted to nicotinamide via indole-3-pyruvic acid (IPA) is very low, this amount of D-Trp is converted to L-Trp, which is primarily used for protein synthesis rather than catabolism via the Kyn biosynthesis pathway in mice
metabolism
the first and rate limiting step of the kynurenine pathway is carried out by two heme-containing enzymes, tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52), which differ in their tissue distribution and regulation
metabolism
weaning alters the tryptophan 2,3-dioxygenase activity by affecting the acetylation state of the enzyme in piglets livers
metabolism
-
comparison of contribution percentage of tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) to the conversion of L-tryptophan, the calculated percentage conversions indicats that TDO and IDO oxidize 70% and 30%, respectively, of the dietary L-tryptophan. The amount of D-Trp converted to nicotinamide via indole-3-pyruvic acid (IPA) is very low, this amount of D-Trp is converted to L-Trp, which is primarily used for protein synthesis rather than catabolism via the Kyn biosynthesis pathway in mice
-
physiological function
tryptophan 2,3-dioxygenase (TDO) is one of the two key enzymes in the kynurenine pathway, it catalyzes the indole ring cleavage at the C2-C3 bond of L-tryptophan. This is a rate-limiting step in the regulation of tryptophan concentration in vivo. In addition to its role in protein synthesis, 95% of L-Trp in the human body is processed by the kynurenine pathway, leading to the production of nicotinamide adenine dinucleotide. Enzyme TDO is expressed in many tumor cells and is related to reduction of antitumor immune response
physiological function
-
tryptophan 2,3-dioxygenase (TDO) has a immunomodulatory function that promotes tumoral immune resistance and proliferation
physiological function
the enzyme is involved in nicotinamide biosynthesis. Comparison of contribution percentage of tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) to the conversion of L-tryptophan, the calculated percentage conversions indicats that TDO and IDO oxidize 70% and 30%, respectively, of the dietary L-tryptophan. The amount of D-Trp converted to nicotinamide via indole-3-pyruvic acid (IPA) is very low, this amount of D-Trp is converted to L-Trp, which is primarily used for protein synthesis rather than catabolism via the Kyn biosynthesis pathway in mice
physiological function
the enzyme is involved in L-tryptophan catabolism to produce bioactive metabolites including kynurenine, kynurenic acid, quinolinic acid, and the coenzyme NAD+ via the kynurenine pathway
physiological function
the human heme enzyme tryptophan 2,3-dioxygenase (hTDO) catalyzes the insertion of dioxygen into its cognate substrate, L-tryptophan (L-Trp)
physiological function
tryptophan 2,3-dioxygenase catalyzes the oxidation of the essential amino acid tryptophan to N-formylkynurenine which is rapidly converted to a series of biological active metabolites including kynurenine via the kynurenine pathway
physiological function
the enzyme is overactivated or overexpressed in many human cancers, which is associated with poor patient outcomes
physiological function
the enzyme plays a key role in regulating the activation of fibroblast-like synoviocytes in autoimmune arthritis
physiological function
-
the kynurenine pathway is the major route of tryptophan metabolism. The first step of this pathway is catalysed by one of two heme-dependent dioxygenase enzymes - tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) - leading initially to the formation of N-formylkynurenine
physiological function
the enzyme catalyses the rate-limiting step in the kynurenine pathway, an important biochemical mechanism for immunological responsecancers express tryptophan catabolising enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2) to produce immunosuppressive tryptophan metabolites that undermine thr immune systems of patients, leading to poor disease outcomes
physiological function
conversion of tryptophan to N-formylkynurenine is the first and rate-limiting step of the tryptophan metabolic pathway (i.e., the kynurenine pathway). This conversion is catalyzed by three enzyme isoforms: indoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), and tryptophan-2,3-dioxygenase (TDO)
physiological function
tryptophanemia is controlled by a tryptophan-sensing mechanism ubiquitinating tryptophan 2,3-dioxygenase. A mechanism allows stable tryptophanemia despite varying levels of tryptophan supply in the diet. High tryptophan availability stabilizes tryptophan 2,3-dioxygenase in the liver, allowing efficient tryptophan catabolism. In contrast, low tryptophan levels trigger proteasome-mediated degradation of tryptophan 2,3-dioxygenase, thereby stopping tryptophan catabolism and preventing hypotryptophanemia
physiological function
TDO2 is the key enzyme responsible for reduced tryptophan levels in mut-MED12 leiomyoma
physiological function
the enzyme (TDO2) catalyzes the conversion of tryptophan to the immunosuppressive metabolite kynurenine
physiological function
tryptophan 2,3-dioxygenase is the rate-limiting enzyme in the kynurenine pathway. It catalyzes the oxidative breakdown of the essential amino acid, L-tryptophan to N-formylkynurenine. This reaction is also carried out by an analogous hemoprotein, indoleamine 2,3-dioxygenase, albeit with a much lower substrate selectivity
physiological function
the first step of the kynurenine pathway for L-tryptophan (L-Trp) degradation is catalyzed by heme-dependent dioxygenases, tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase
physiological function
tryptophan 2,3-dioxygenase is a key enzyme of tryptophan metabolism at the entry of the kynurenine pathway which moderates production of neuroactive compounds primarily outside the central nervous system
physiological function
the enzyme is responsible for L-tryptophan (L-Trp) homeostasis. Expression of TDO2 in cancer cells results in the inhibition of immune-mediated tumor rejection due to an enhancement of L-Trp catabolism via the kynurenine pathway
physiological function
the enzyme plays a key role in regulating the activation of fibroblast-like synoviocytes in autoimmune arthritis
physiological function
-
the enzyme is involved in nicotinamide biosynthesis. Comparison of contribution percentage of tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO, EC 1.13.11.52) to the conversion of L-tryptophan, the calculated percentage conversions indicats that TDO and IDO oxidize 70% and 30%, respectively, of the dietary L-tryptophan. The amount of D-Trp converted to nicotinamide via indole-3-pyruvic acid (IPA) is very low, this amount of D-Trp is converted to L-Trp, which is primarily used for protein synthesis rather than catabolism via the Kyn biosynthesis pathway in mice
-
physiological function
-
the first step of the kynurenine pathway for L-tryptophan (L-Trp) degradation is catalyzed by heme-dependent dioxygenases, tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase
-
additional information
eight residues play critical roles in L-tryptophan oxidation, i.e. Y42, Y45, F72, H76, F140, R144, S151, and H328. hTDO must form an oligomer to exhibit activity
additional information
-
eight residues play critical roles in L-tryptophan oxidation, i.e. Y42, Y45, F72, H76, F140, R144, S151, and H328. hTDO must form an oligomer to exhibit activity
additional information
no evidence for the accumulation of Compound II during TDO catalysis, instead a ternary [Fe(II)-O2, L-Trp] complex is detected under steady state conditions. Absence of a Compound II species in the steady state in TDO is not due to an intrinsic inability of the TDO enzyme to form ferryl heme, because Compound II can be formed directly through a different route in which ferrous heme is reacted with peroxide
additional information
no evidence for the accumulation of Compound II during TDO catalysis, instead a ternary [Fe(II)-O2, L-Trp] complex is detected under steady state conditions. Absence of a Compound II species in the steady state in TDO is not due to an intrinsic inability of the TDO enzyme to form ferryl heme, because Compound II can be formed directly through a different route in which ferrous heme is reacted with peroxide
additional information
-
no evidence for the accumulation of Compound II during TDO catalysis, instead a ternary [Fe(II)-O2, L-Trp] complex is detected under steady state conditions. Absence of a Compound II species in the steady state in TDO is not due to an intrinsic inability of the TDO enzyme to form ferryl heme, because Compound II can be formed directly through a different route in which ferrous heme is reacted with peroxide
-
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
tetramer
additional information
tetramer
holo-hTDO, dimer of dimers, in which the two C-shape dimers (AB and CD) are clamped perpendicularly to each other to form a tight tetramer
tetramer
4 * 48000, high tryptophan levels stabilize the active tetrameric conformation of the enzyme through binding noncatalytic exosites. The lack of tryptophan binding in the exosites destabilizes the tetramer into inactive monomers and dimers
additional information
hTDO must form an oligomer to exhibit activity. Active site structure, overview
additional information
-
hTDO must form an oligomer to exhibit activity. Active site structure, overview
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
acetylation
weaning exacerbates the deacetylation of tryptophan 2,3-dioxygenase. Weaning alters the tryptophan 2,3-dioxygenase activity by affecting the acetylation state of the enzyme in piglets livers
ubiquitination
ubiquitination
in low tryptophan, the lack of tryptophan binding in the exosites destabilizes the tetramer into inactive monomers and dimers and unmasks a four-amino acid degron that triggers polyubiquitination of tryptophan 2,3-dioxygenase by SKP1-CUL1-F-box complexes, resulting in proteasome-mediated degradation of the enzyme and rapid interruption of tryptophan catabolism
ubiquitination
the enzyme can be recognized and ubiquitinated by two E3 ubiquitin ligases, gp78/AMFR and CHIP, and subsequently degraded via ubiquitin-dependent proteasomal degradation pathway. 15 ubiquitination K-sites are identified. Trp-binding to an exosite impedes its proteolytic degradation
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified enzyme in a ternary complex with the substrates L-Trp and O2 and in a binary complex with the product N-formylkynurenine, under-oil microbatch method under anaerobic conditions, mixing of 0.003 ml of 45 mg/ml protein in 50 mM Tris, pH 8.0, containing 150 mM NaCl and 10 mM L-Trp, and reduced with 2-fold molar excess of sodium dithionite, with 0.003-0.006 ml of precipitannt solution containing 50 mM sodium citrate, pH 5.6, 5% w/v PEG 3350, and 2% w/v Tacsimate, pH 5.0, X-ray diffraction structure determination and analysis at 2.5 A and 2.44 A resolution, respectively. Crystals of the Trp-bound binary complex are soaked in an O2-saturated precipitant solution supplemented with 20% v/v ethylene glycol at room temperature
purified full-length and truncated enzyme variants without heme cofactor, hanging drop vapor diffusion method, mixing of 0.001 ml of 20 mg/ml protein in 100 mM TrisHCl, pH 8.0, with 0.001 ml of reservoir solution containing 0.1 M sodium cacodylate, pH 6.0-6.5, 6-10% w/v MPEG 5000, and 10% v/v 2-propanol, addition of hexammine cobalt(III) chloride improves the diffraction significantly, 16°C, X-ray diffraction structure determination and analysis at 2.90 A resolution
crystal structure of the enzyme in complex with L-kynurenine
crystal structure of the enzyme in complex with L-kynurenine
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
F140A
site-directed mutagenesis, the mutant shows 0.25% of wild-type activity
R144A
site-directed mutagenesis, the mutant shows 0.88% of wild-type activity
S151A
site-directed mutagenesis, the mutant shows 9.08% of wild-type activity
Y175G
site-directed mutagenesis, the mutation leads to a 6fold slower multiple turnover velocity. In addition, pre-incubation of the Y175G mutant with 8 mM NFK retards the formation of the ternary complex by about 100fold and impedes Trp binding
Y42A
site-directed mutagenesis, the mutant shows 0.5% of wild-type activity
Y45A
site-directed mutagenesis, the mutant shows 1.13% of wild-type activity
2 F51S/T254S
-
variant synthesizes monooxigenation product 3alpha-hydroxyhexahydropyrrolo[2,3-b]indole-2-carboxylic acid in a ratio of 6.2:1 to wild-type product N-formyl-L-kynurenine
3 F51Q/G255S
-
variant synthesizes monooxigenation product 3alpha-hydroxyhexahydropyrrolo[2,3-b]indole-2-carboxylic acid in a ratio of 3.1:1 to wild-type product N-formyl-L-kynurenine
4 F51M/Q127Y/T254S
-
variant synthesizes monooxigenation product 3alpha-hydroxyhexahydropyrrolo[2,3-b]indole-2-carboxylic acid in a ratio of 2.6:1 to wild-type product N-formyl-L-kynurenine
F51I/Q127Y
-
mutant F51M/Q127Y shows higher 3alpha-hydroxyhexahydropyrrolo[2,3-b]indole-2-carboxylic acid productivity than mutant F51I/Q127Y and mutant F51L/Q127Y, suggesting that the F51M and Q127Y substitutions imposed a cooperative effect on the enzyme activity
F51L/Q127Y
-
mutant F51M/Q127Y shows higher 3alpha-hydroxyhexahydropyrrolo[2,3-b]indole-2-carboxylic acid productivity than mutant F51I/Q127Y and mutant F51L/Q127Y, suggesting that the F51M and Q127Y substitutions imposed a cooperative effect on the enzyme activity
F51M/Q127Y
F51M/Q127Y/T254S
-
mutations result in a decrease in the turnover numbers for production of 3alpha-hydroxyhexahydropyrrolo[2,3-b]indole-2-carboxylic acid
F51Q/G255S
-
mutation enhances the 3alpha-hydroxyhexahydropyrrolo[2,3-b]indole-2-carboxylic acid/N'-formylkynurenine ratio to 3.1:1
F51X
-
F51X mutant plasmids that express enzyme proteins with turnover numbers greater than 250 are used as templates to further improve production of 3alpha-hydroxyhexahydropyrrolo[2,3-b]indole-2-carboxylic acid
TDOF51S/T254S
-
mutation enhances the 3alpha-hydroxyhexahydropyrrolo[2,3-b]indole-2-carboxylic acid/N'-formylkynurenine ratio to 6.2:1
additional information
F51M/Q127Y
-
mutant F51M/Q127Y shows higher 3alpha-hydroxyhexahydropyrrolo[2,3-b]indole-2-carboxylic acid productivity than mutant F51I/Q127Y and mutant F51L/Q127Y, suggesting that the F51M and Q127Y substitutions imposed a cooperative effect on the enzyme activity
F51M/Q127Y
-
variant synthesizes monooxigenation product 3alpha-hydroxyhexahydropyrrolo[2,3-b]indole-2-carboxylic acid in a ratio of 2.0:1 to wild-type product N-formyl-L-kynurenine
additional information
full-length hTDO is unstable, and various truncations are constructed. A truncation containing amino acids 19-388 is found to have good solubility and stability, the truncated mutant shows 80.45% of wild-type activity
additional information
-
full-length hTDO is unstable, and various truncations are constructed. A truncation containing amino acids 19-388 is found to have good solubility and stability, the truncated mutant shows 80.45% of wild-type activity
additional information
construction of TDO-knockout mice, phenotype, overview. The amount of D-Trp converted to nicotinamide via indole-3-pyruvic acid (IPA) is very low
additional information
-
construction of TDO-knockout mice, phenotype, overview. The amount of D-Trp converted to nicotinamide via indole-3-pyruvic acid (IPA) is very low
-
additional information
-
directed evolution of a tryptophan 2,3-dioxygenase for the diastereoselective monooxygenation of tryptophans
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
high tryptophan levels stabilize the active tetrameric conformation of the enzyme through binding noncatalytic exosites, resulting in rapid catabolism of tryptophan
in low tryptophan, the lack of tryptophan binding in the exosites destabilizes the tetramer into inactive monomers and dimers
one of the most rapidly degraded liver proteins with a half-life (t1/2) of about 2.3 h, relative to an average t1/2 of about 2-3 days for total liver protein
the nonmetabolizable analog alpha-methyl-tryptophan stabilizes tetrameric enzyme and thereby stably reduces tryptophanemia
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
recombinant N-terminally His6-tagged wild-type and mutant enzymes from Escherichia coli BL21(DE3) by nickel affinity chromatography and gel filtration
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene 33737, DNA and amino acid sequence determination and analysis, sequence and genetic structure comparisons, and phylogenetic analysis, functional complementation of the enzyme-deficient Saccharomyces cerevisiae
gene BRAFLDRAFT_210874, DNA and amino acid sequence determination and analysis, sequence and genetic structure comparisons, and phylogenetic analysis, functional complementation of the enzyme-deficient Saccharomyces cerevisiae
gene C28H8.11, DNA and amino acid sequence determination and analysis, sequence and genetic structure comparisons, and phylogenetic analysis, functional complementation of the enzyme-deficient Saccharomyces cerevisiae
gene kynA, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)
gene TDO, DNA and amino acid sequence determination and analysis, sequence and genetic structure comparisons, and phylogenetic analysis, functional complementation of the enzyme-deficient Saccharomyces cerevisiae
gene TDO, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)
gene TDO2, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)
gene TDOa, DNA and amino acid sequence determination and analysis, sequence and genetic structure comparisons, and phylogenetic analysis, functional complementation of the enzyme-deficient Saccharomyces cerevisiae
-
gene v1g157887, DNA and amino acid sequence determination and analysis, sequence and genetic structure comparisons, and phylogenetic analysis, recombinant expression of His6-tagged enzyme in Escherichia coli strain KRX, functional complementation of the enzyme-deficient Saccharomyces cerevisiae
gene vCG5163, DNA and amino acid sequence determination and analysis, sequence and genetic structure comparisons, and phylogenetic analysis, functional complementation of the enzyme-deficient Saccharomyces cerevisiae
recombinant expression of full-length His6-tagged hTDO protein in human liver HepG2 cell culture
recombinant expression of N-terminally His6-tagged wild-type and mutant enzymes in Escherichia coli BL21(DE3)
gene TDO, DNA and amino acid sequence determination and analysis, sequence and genetic structure comparisons, and phylogenetic analysis, functional complementation of the enzyme-deficient Saccharomyces cerevisiae
gene TDO, DNA and amino acid sequence determination and analysis, sequence and genetic structure comparisons, and phylogenetic analysis, functional complementation of the enzyme-deficient Saccharomyces cerevisiae
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression is strongly increased in synovial tissue and fibroblast-like synoviocytes of rheumatoid arthritis and adjuvant-induced arthritis. Immune cells express high amount of the enzyme (TDO2) at the peak stage of adjuvant-induced arthritis
TDO2 gene expression is upregulated in leiomyoma expressing mut-MED12. The tissue mRNA levels of tryptophan 2,3-dioxygenase (TDO2), the rate limiting enzyme of tryptophan metabolism through the kynurenine pathway, is 36fold higher in leiomyomas expressing mutated mediator complex subunit 12 (mut-MED12) compared to adjacent myometrium, and 14fold higher compared to wild type-MED12 leiomyoma
expression is strongly increased in synovial tissue and fibroblast-like synoviocytes of rheumatoid arthritis and adjuvant-induced arthritis. Immune cells express high amount of the enzyme (TDO2) at the peak stage of adjuvant-induced arthritis
expression is strongly increased in synovial tissue and fibroblast-like synoviocytes of rheumatoid arthritis and adjuvant-induced arthritis. Immune cells express high amount of the enzyme (TDO2) at the peak stage of adjuvant-induced arthritis
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Basran, J.; Booth, E.S.; Lee, M.; Handa, S.; Raven, E.L.
Analysis of reaction intermediates in tryptophan 2,3-dioxygenase a comparison with indoleamine 2,3-dioxygenase
Biochemistry
55
6743-6750
2016
Homo sapiens (P48775), Xanthomonas campestris pv. campestris (Q8PDA8), Xanthomonas campestris pv. campestris ATCC 33913 (Q8PDA8)
brenda
Maeta, A.; Sano, M.; Fukuwatari, T.; Funakoshi, H.; Nakamura, T.; Shibata, K.
Contributions of tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase to the conversion of D-tryptophan to nicotinamide analyzed by using tryptophan 2,3-dioxygenase-knockout mice
Biosci. Biotechnol. Biochem.
78
878-881
2014
Mus musculus (P48776), Mus musculus C57BL/6 (P48776)
brenda
Pantouris, G.; Loudon-Griffiths, J.; Mowat, C.G.
Insights into the mechanism of inhibition of tryptophan 2,3-dioxygenase by isatin derivatives
J. Enzyme Inhib. Med. Chem.
31
70-78
2016
Homo sapiens
brenda
Yuasa, H.J.; Ball, H.J.
Efficient tryptophan-catabolizing activity is consistently conserved through evolution of TDO enzymes, but not IDO enzymes
J. Exp. Zool. B
324
128-140
2015
Branchiostoma floridae (C3XXE6), Caenorhabditis elegans (Q09474), Drosophila melanogaster (P20351), Homo sapiens (P48775), Monosiga brevicollis (A9V766), Nematostella vectensis (A7RFF0), no activity in Brugia malayi, no activity in Saccharomyces cerevisiae, no activity in Schistosoma mansoni, Rattus norvegicus (P21643), Strongylocentrotus purpuratus
brenda
Wu, J.S.; Lin, S.Y.; Liao, F.Y.; Hsiao, W.C.; Lee, L.C.; Peng, Y.H.; Hsieh, C.L.; Wu, M.H.; Song, J.S.; Yueh, A.; Chen, C.H.; Yeh, S.H.; Liu, C.Y.; Lin, S.Y.; Yeh, T.K.; Hsu, J.T.; Shih, C.; Ueng, S.H.; Hung, M.S.; Wu, S.Y.
Identification of substituted naphthotriazolediones as novel tryptophan 2,3-dioxygenase (TDO) inhibitors through structure-based virtual screening
J. Med. Chem.
58
7807-7819
2015
Homo sapiens (P48775)
brenda
Nienhaus, K.; Hahn, V.; Huepfel, M.; Nienhaus, G.U.
Substrate binding primes human tryptophan 2,3-dioxygenase for ligand binding
J. Phys. Chem. B
121
7412-7420
2017
Homo sapiens (P48775), Homo sapiens
brenda
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
Xanthomonas campestris pv. campestris (Q8PDA8), Homo sapiens (P48775), Homo sapiens (P14902), Homo sapiens (Q6ZQW0), Mus musculus (P28776), Xanthomonas campestris pv. campestris ATCC 33913 (Q8PDA8)
brenda
Meng, B.; Wu, D.; Gu, J.; Ouyang, S.; Ding, W.; Liu, Z.
Structural and functional analyses of human tryptophan 2,3-dioxygenase
Proteins
82
3210-3216
2014
Homo sapiens (P48775), Homo sapiens
brenda
Lewis-Ballester, A.; Forouhar, F.; Kim, S.M.; Lew, S.; Wang, Y.; Karkashon, S.; Seetharaman, J.; Batabyal, D.; Chiang, B.Y.; Hussain, M.; Correia, M.A.; Yeh, S.R.; Tong, L.
Molecular basis for catalysis and substrate-mediated cellular stabilization of human tryptophan 2,3-dioxygenase
Sci. Rep.
6
35169
2016
Homo sapiens (P48775), Homo sapiens
brenda
Pei, Z.; Mendonca, R.; Gazzard, L.; Pastor, R.; Goon, L.; Gustafson, A.; VanderPorten, E.; Hatzivassiliou, G.; Dement, K.; Cass, R.; Yuen, P.W.; Zhang, Y.; Wu, G.; Lin, X.; Liu, Y.; Sellers, B.D.
Aminoisoxazoles as potent inhibitors of tryptophan 2,3-dioxygenase 2 (TDO2)
ACS Med. Chem. Lett.
9
417-421
2018
Homo sapiens (P48775), Homo sapiens
brenda
Wei, Y.; Lu, C.; Jiang, S.; Zhang, Y.; Li, Q.; Bai, W.J.; Wang, X.
Directed evolution of a tryptophan 2,3-dioxygenase for the diastereoselective monooxygenation of tryptophans
Angew. Chem. Int. Ed. Engl.
59
3043-3047
2020
Xanthomonas campestris
brenda
Liu, Y.; Kim, S.M.; Wang, Y.; Karkashon, S.; Lewis-Ballester, A.; Yeh, S.R.; Correia, M.A.
Characterization of the structural determinants of the ubiquitin-dependent proteasomal degradation of human hepatic tryptophan 2,3-dioxygenase
Biochem. J.
478
1999-2017
2021
Homo sapiens (P48775), Homo sapiens
brenda
Geng, J.; Weitz, A.C.; Dornevil, K.; Hendrich, M.P.; Liu, A.
Kinetic and spectroscopic characterization of the catalytic ternary complex of tryptophan 2,3-dioxygenase
Biochemistry
59
2813-2822
2020
Cupriavidus metallidurans (Q1LK00), Cupriavidus metallidurans, Cupriavidus metallidurans ATCC 43123 (Q1LK00)
brenda
Zhang, S.; Guo, L.; Yang, D.; Xing, Z.; Li, W.; Kuang, C.; Yang, Q.
Evaluation and comparison of the commonly used bioassays of human indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO)
Bioorg. Chem.
104
104348
2020
Homo sapiens (P48775), Homo sapiens
brenda
Li, Y.; Zhang, S.; Wang, R.; Cui, M.; Liu, W.; Yang, Q.; Kuang, C.
Synthesis of novel tryptanthrin derivatives as dual inhibitors of indoleamine 2,3-dioxygenase 1 and tryptophan 2,3-dioxygenase
Bioorg. Med. Chem. Lett.
30
127159
2020
Homo sapiens (P48775)
brenda
Chang, Y.; Han, P.; Wang, Y.; Jia, C.; Zhang, B.; Zhao, Y.; Li, S.; Li, S.; Wang, X.; Yang, X.; Wei, W.
Tryptophan 2,3-dioxygenase 2 plays a key role in regulating the activation of fibroblast-like synoviocytes in autoimmune arthritis
Br. J. Pharmacol.
179
3024-3042
2022
Homo sapiens (P48775), Rattus norvegicus (P21643)
brenda
Boros, F.A.; Vecsei, L.
Tryptophan 2,3-dioxygenase, a novel therapeutic target for Parkinsons disease
Expert Opin. Ther. Targets
25
877-888
2021
Homo sapiens (P48775)
brenda
Basran, J.; Booth, E.S.; Campbell, L.P.; Thackray, S.J.; Jesani, M.H.; Clayden, J.; Moody, P.C.E.; Mowat, C.G.; Kwon, H.; Raven, E.L.
Binding of L-kynurenine to X. campestris tryptophan 2,3-dioxygenase
J. Inorg. Biochem.
225
111604
2021
Xanthomonas campestris pv. campestris (Q8PDA8), Xanthomonas campestris, Xanthomonas campestris pv. campestris ATCC 33913 (Q8PDA8)
brenda
Kozlova, A.; Thabault, L.; Liberelle, M.; Klaessens, S.; Prevost, J.R.C.; Mathieu, C.; Pilotte, L.; Stroobant, V.; Van den Eynde, B.; Frederick, R.
Rational design of original fused-cycle selective inhibitors of tryptophan 2,3-dioxygenase
J. Med. Chem.
64
10967-10980
2021
Homo sapiens (P48775)
brenda
Ning, X.L.; Li, Y.Z.; Huo, C.; Deng, J.; Gao, C.; Zhu, K.R.; Wang, M.; Wu, Y.X.; Yu, J.L.; Ren, Y.L.; Luo, Z.Y.; Li, G.; Chen, Y.; Wang, S.Y.; Peng, C.; Yang, L.L.; Wang, Z.Y.; Wu, Y.; Qian, S.; Li, G.B.
X-ray structure-guided discovery of a potent, orally bioavailable, dual human indoleamine/tryptophan 2,3-dioxygenase (hIDO/hTDO) inhibitor that shows activity in a mouse model of Parkinsons disease
J. Med. Chem.
64
8303-8332
2021
Homo sapiens (P48775), Homo sapiens
brenda
Huang, L.; Yao, W.; Wang, T.; Li, J.; He, Q.; Huang, F.
Acetylation of phenylalanine hydroxylase and tryptophan 2,3-dioxygenase alters hepatic aromatic amino acid metabolism in weaned piglets
Metabolites
10
146
2020
Sus scrofa (F1RWA8)
brenda
Sari, S.; Tomek, P.; Leung, E.; Reynisson, J.
Discovery and characterisation of dual inhibitors of tryptophan 2,3-dioxygenase (TDO2) and indoleamine 2,3-dioxygenase 1 (IDO1) using virtual screening
Molecules
24
4346
2019
Homo sapiens (P48775), Homo sapiens
brenda
Dolsak, A.; Gobec, S.; Sova, M.
Indoleamine and tryptophan 2,3-dioxygenases as important future therapeutic targets
Pharmacol. Ther.
221
107746
2021
Homo sapiens, Homo sapiens (P14902), Homo sapiens (Q6ZQW0)
brenda
Klaessens, S.; Stroobant, V.; Hoffmann, D.; Gyrd-Hansen, M.; Pilotte, L.; Vigneron, N.; De Plaen, E.; Van den Eynde, B.J.
Tryptophanemia is controlled by a tryptophan-sensing mechanism ubiquitinating tryptophan 2,3-dioxygenase
Proc. Natl. Acad. Sci. USA
118
e2022447118
2021
Homo sapiens (P48775)
brenda
Hutchinson, A.P.; Yin, P.; Neale, I.; Coon, J.S.; Kujawa, S.A.; Liu, S.; Bulun, S.E.
Tryptophan 2,3-dioxygenase-2 in uterine Leiomyoma dysregulation by MED12 mutation status
Reprod. Sci.
29
743-749
2022
Homo sapiens (P48775)
brenda
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