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Information on EC 1.13.11.52 - indoleamine 2,3-dioxygenase and Organism(s) Rattus norvegicus and UniProt Accession Q9ERD9
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1.13.11.52 indoleamine 2,3-dioxygenaseIUBMB Comments
A protohemoprotein. Requires ascorbic acid and methylene blue for activity. This enzyme has broader substrate specificity than EC 1.13.11.11, tryptophan 2,3-dioxygenase . It is induced in response to pathological conditions and host-defense mechanisms and its distribution in mammals is not confined to the liver . While the enzyme is more active with D-tryptophan than L-tryptophan, its only known function to date is in the metabolism of L-tryptophan [2,6]. Superoxide radicals can replace O2 as oxygen donor [4,7].
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Word Map
- 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
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
indoleamine 2,3-dioxygenase, indoleamine-2,3-dioxygenase, tryptophan pyrrolase, tryptophan oxygenase, indoleamine 2,3 dioxygenase, indoleamine 2,3-dioxygenase-1, indolamine 2,3-dioxygenase, tryptophan dioxygenase, hido1, indoleamine-pyrrole 2,3-dioxygenase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
indolamine 2,3-dioxygenase
-
-
-
-
indoleamine 2,3-dioxygenase
-
-
-
-
L-tryptophan pyrrolase
-
-
-
-
oxygenase, tryptophan 2,3-di-
-
-
-
-
superoxygenase
-
-
-
-
TDO
TO
-
-
-
-
TRPO
-
-
-
-
Tryptamin 2,3-dioxygenase
-
-
-
-
tryptamine 2,3-dioxygenase
-
-
-
-
tryptophan oxygenase
-
-
-
-
tryptophan peroxidase
-
-
-
-
tryptophan pyrrolase
-
-
-
-
tryptophanase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
D-tryptophan:oxygen 2,3-oxidoreductase (decyclizing)
A protohemoprotein. Requires ascorbic acid and methylene blue for activity. This enzyme has broader substrate specificity than EC 1.13.11.11, tryptophan 2,3-dioxygenase [1]. It is induced in response to pathological conditions and host-defense mechanisms and its distribution in mammals is not confined to the liver [2]. While the enzyme is more active with D-tryptophan than L-tryptophan, its only known function to date is in the metabolism of L-tryptophan [2,6]. Superoxide radicals can replace O2 as oxygen donor [4,7].
CAS REGISTRY NUMBER
COMMENTARY
9014-51-1
-
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
additional information
additional information
-
-
no activity with D-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
-
no activity with oxygen concentrations below 0.1 mM, maximum activity at 1.15 mM oxygen
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
-
rate-limiting enzyme in L-tryptophan catabolism and thus a key serotonergic determinant
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
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
-
no activity with oxygen concentrations below 0.1 mM, maximum activity at 1.15 mM oxygen
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
-
rate-limiting enzyme in L-tryptophan catabolism and thus a key serotonergic determinant
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
heme
-
the ferric form of the enzyme shows magnetic CD spectra ascribable to a high spin protohemoprotein at neutral pH
heme
-
the already active reduced holoenzyme does not require haematin for activity, the heme-free predominant apoenzyme does
heme
-
TDO is regulated by heme, its prosthetic moiety, as its expression and function are significantly reduced after acute hepatic heme depletion
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
copper
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
acetaminophen
-
no affect on holoenzyme, significant inhibition of apoenzyme, changes in brain serotonin levels due to inhibition of hepatic tryptophan 2,3-dioxygenase
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ascorbic acid
-
tryptophan 2,3-dioxygenase: maximal activity at 10 mM ascorbate
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
420 per min, formylkynurenine formed
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.000192
-
L-tryptophan, Tris-buffer, pH 8.0, 0.0001 mM methylene blue and 0.001 mM each of ATP and Mg2+, 37°C, 90 min, no rat-pretreatment
0.000208
-
D-tryptophan, Tris-buffer, pH 8.0, 0.0001 mM methylene blue and 0.001 mM each of ATP and Mg2+, 37°C, 90 min, no rat-pretreatment
0.000224
-
D-tryptophan, Tris-buffer, pH 8.0, 0.0001 mM methylene blue and 0.001 mM each of ATP and Mg2+, 37°C, 90 min, rat-pretreatment with neomycin
0.000245
-
L-tryptophan, Tris-buffer, pH 8.0, 0.0001 mM methylene blue and 0.001 mM each of ATP and Mg2+, 37°C, 90 min, rat-pretreatment with cortisone
0.000256
-
D-tryptophan, Tris-buffer, pH 8.0, 0.0001 mM methylene blue and 0.001 mM each of ATP and Mg2+, 37°C, 90 min, rat-pretreatment with cortisone
0.000272
-
L-tryptophan, Tris-buffer, pH 8.0, 0.0001 mM methylene blue and 0.001 mM each of ATP and Mg2+, 37°C, 90 min, rat-pretreatment with D-tryptophan
0.000277
-
D-tryptophan, Tris-buffer, pH 8.0, 0.0001 mM methylene blue and 0.001 mM each of ATP and Mg2+, 37°C, 90 min, rat-pretreatment with D-tryptophan
0.145
-
small intestine, in 5.2 atm oxygen, 50 mM potassium phosphate buffer, pH 6.5, 0.025 mM methylene blue, 20 mM ascorbate, 0.05 mM catalase, 0.4 mM L-tryptophan, 37°C
0.24
-
small intestine, in 1.2 atm oxygen, 50 mM potassium phosphate buffer, pH 6.5, 0.025 mM methylene blue, 20 mM ascorbate, 0.05 mM catalase, 0.4 mM L-tryptophan, 37°C
0.38
-
small intestine, in air, 50 mM potassium phosphate buffer, pH 6.5, 0.025 mM methylene blue, 20 mM ascorbate, 0.05 mM catalase, 0.4 mM L-tryptophan, 37°C
additional information
additional information
-
influence of some methodological factors on measurement of tryptophan oxygenase activities in crude homogenates of rat liver
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
intestinal mucosa of rat exhibits lower activity than in rabbit
-
in the group of rats aged 12 months, the highest specific activity is found in the small intestine
-
-
395456, 395464, 395470, 395476, 395477, 395479, 395481, 395486, 395488, 395489, 395497, 658924, 663910, 666138, 688601, 699980
-
activity is low in newborn rats, increases up to the age of 2-3 months and decreases from 3 months of age to 18 months
-
in newborn rats IDO activity is present only in small intestine. In the group of rats aged 2-3 months, the highest specific activity is found in the small intestine, decrease of enzyme activity in relation to age
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
-
IDO-expressing skin substitutes significantly suppress T cell infiltration and improve neovascularization by 4fold
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). I23O1_RAT
407
0
45831
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
167000
167000
-
gel filtration, sucrose density gradient centrifugation, equilibrium sedimentation
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
a 46000 Da species and a 49000 Da species are detected by SDS-PAGE. The 46000 Da species is shorter than the 49000 Da species by 19 amino acid residues including six His residues at the end. A limited proteolysis appears to occur between Tyr13 and Thr14 of the original polypeptide chain
tetramer
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
enzyme is most stable in presence of L-Trp or alpha-methyl-DL-tryptophan, and in absence of oxygen
-
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-9°C, pH 7, stable in 0.1 M phosphate buffer with Trp and DTT, for at least 2 weeks
-
pH 7.0, anaerobically stored in 0.1 M potassium phosphate buffer containing L-Trp, quite stable
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
tissues thawed at room temperature, homogenized in 0.14 M potassium chloride plus 20 mM potassium phosphate, pH 7.0
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
construction of a cDNA clone and its use in isolating genomic clones containing the structural gene
-
enzyme with a His tag at the N-terminus is expressed in Escherichia coli JM109 harboring plasmid pUC18 carrying the full-length cDNA of TDO
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
engraftment of IDO expressing skin substitutes on the back of rats significantly improves healing progression over 7 days compared with both nontreated and non-IDO-expressing skin substitutes
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Badawy, A.A.
Central role of tryptophan pyrrolase in haem metabolism
Biochem. Soc. Trans.
7
575-583
1979
Bos taurus, Cavia porcellus, Gallus gallus, Oryctolagus cuniculus, Felis catus, Frog, Meriones unguiculatus, Cricetinae, Ovis aries, Homo sapiens, Meleagris gallopavo, Mus musculus, Rattus norvegicus, Sus scrofa
Feigelson, P.; Brady, F.O.
Heme-containing dioxygenases
Mol. Mech. Oxygen Activ. (Hayaishi, O., ed.) Academic Press, New York
87-133
1974
Delftia acidovorans, Rattus norvegicus
-
Maezono, K.; Tashiro, K.; Nakamura, T.
Deduced primary structure of rat tryptophan-2,3-dioxygenase
Biochem. Biophys. Res. Commun.
170
176-181
1990
Rattus norvegicus, Rattus norvegicus (P21643)
Uchida, K.; Shimizu, T.; Makino, R.; Sakaguchi, K.; Iizuka, T.; Ishimura, Y.
Magnetic and natural circular dichroism of L-tryptophan 2,3-dioxygenases and indoleamine 2,3-dioxygenase. I. Spectra of ferric and ferrous high spin forms
J. Biol. Chem.
258
2519-2525
1983
Delftia acidovorans, Oryctolagus cuniculus, Rattus norvegicus
Salter, M.; Hazelwood, R.; Pogson, C.I.; Iyer, R.; Madge, D.J.
The effects of a novel and selective inhibitor of tryptophan 2,3-dioxygenase on tryptophan and serotonin metabolism in the rat
Biochem. Pharmacol.
49
1435-1442
1995
Rattus norvegicus
Dang, Y.; Dale, W.E.; Brown, O.R.
Comparative effects of oxygen on indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase of the kynurenine pathway
Free Radic. Biol. Med.
28
615-624
2000
Meriones unguiculatus, Rattus norvegicus
Dick, R.; Murray, B.P.; Reid, M.J.; Correia, M.A.
Structure-Function Relationships of Rat Hepatic Tryptophan 2,3-Dioxygenase: Identification of the Putative Heme-Ligating Histidine Residues
Arch. Biochem. Biophys.
392
71-78
2001
Rattus norvegicus
Stowell, L.; Morland, J.
The influence of some methodological factors on measurement of tryptophan oxygenase activities in crude homogenates of rat liver
Biochem. J.
209
831-836
1983
Rattus norvegicus
Schmid, W.; Scherer, G.; Danesch, U.; Zentgraf, H.; Matthias, P.; Strange, C.M.; Roewekamp, W.; Schuetz, G.
Isolation and characterization of the rat tryptophan oxygenase gene
EMBO J.
1
1287-1293
1982
Rattus norvegicus
Ishimura, Y.; Makino, R.; Iizuka, T.
Regulatory control and catalytic mechanisms of L-tryptophan 2,3-dioxygenase (pyrrolase)
Adv. Enzyme Regul.
18
291-302
1980
Oryctolagus cuniculus, Pseudomonas sp., Rattus norvegicus
Rouach, H.; Ribiere, C.; Nordmann, J.; Nordmann, R.
In vitro inhibition of rat liver tryptophan oxygenase by 4-hydroxypyrazole
FEBS Lett.
101
149-152
1979
Rattus norvegicus
Ren, S.; Liu, H.; Licad, E.; Correia, M.A.
Expression of rat liver tryptophan 2,3-dioxygenase in Escherichia coli: structural and functional characterization of the purified enzyme
Arch. Biochem. Biophys.
333
96-102
1996
Rattus norvegicus
Schutz, G.; Feigelson, P.
Purification and properties of rat liver tryptophan oxygenase
J. Biol. Chem.
247
5327-5332
1972
Rattus norvegicus
Brady, F.O.; Monaco, M.E.; Forman, H.J.; Schutz, G.; Feigelson, P.
On the role of copper in activation of and catalysis by tryptophan-2,3-dioxygenase
J. Biol. Chem.
247
7915-7922
1972
Delftia acidovorans, Rattus norvegicus
Knox, W.E.; Yip, A.; Reshef, L.
L-Tryptophan 2,3-dioxygenase (tryptophan pyrrolase) (rat liver)
Methods Enzymol.
17A
415-421
1970
Rattus norvegicus
-
Schimke, R.T.
L-Tryptophan 2,3-dioxygenase (tryptophan pyrrolase) (rat liver)
Methods Enzymol.
17A
421-428
1970
Rattus norvegicus
-
Ishiguro, I.; Naito, J.; Saito, K.; Nagamura, Y.
Skin L-tryptophan-2,3-dioxygenase and rat hair growth
FEBS Lett.
329
178-182
1993
Rattus norvegicus
Daya, S.; Anoopkumar-Dukie, S.
Acetaminophen inhibits liver trytophan-2,3-dioxygenase activity with a concomitant rise in brain serotonin levels and a reduction in urinary 5-hydroxyindole acetic acid
Life Sci.
67
235-240
2000
Rattus norvegicus
Manandhar, S.P.; Shimada, H.; Nagano, S.; Egawa, T.; Ishimura, Y.
Subunit structure of recombinant rat liver L-tryptophan 2,3-dioxygenase
Int. Congr. Ser.
1233
161-169
2002
Rattus norvegicus
-
Watanabe, Y.; Fujiwara, M.; Yoshida, R.; Hayaishi, O.
Stereospecificity of hepatic L-tryptophan 2,3-dioxygenase
Biochem. J.
189
393-405
1980
Bos taurus, Capra hircus, Oryctolagus cuniculus, Homo sapiens, Macaca fuscata fuscata, Mus musculus, Pseudomonas fluorescens, Rattus norvegicus, Sus scrofa
Loh, H.H.; Berg, C.P.
D-Tryptophan pyrrolase activity in the liver and the intestine of the rat
J. Nutr.
102
1331-1339
1972
Rattus norvegicus
Comai, S.; Costa, C.V.; Ragazzi, E.; Bertazzo, A.; Allegri, G.
The effect of age on the enzyme activities of tryptophan metabolism along the kynurenine pathway in rats
Clin. Chim. Acta
360
67-80
2005
Rattus norvegicus
Comai, S.; Bertazzo, A.; Ragazzi, E.; Caparrotta, L.; Costa, C.V.; Allegri, G.
Influence of age on Cu/Zn-superoxide dismutase and indole 2,3-dioxygenase activities in rat tissues
Ital. J. Biochem.
54
232-239
2006
Rattus norvegicus
Yuasa, H.J.; Takubo, M.; Takahashi, A.; Hasegawa, T.; Noma, H.; Suzuki, T.
Evolution of vertebrate indoleamine 2,3-dioxygenases
J. Mol. Evol.
65
705-714
2007
Homo sapiens (P14902), Mus musculus (P28776), Mus musculus, Rattus norvegicus (Q9ERD9)
Liao, M.; Pabarcus, M.K.; Wang, Y.; Hefner, C.; Maltby, D.A.; Medzihradszky, K.F.; Salas-Castillo, S.P.; Yan, J.; Maher, J.J.; Correia, M.A.
Impaired dexamethasone-mediated induction of tryptophan 2,3-dioxygenase in heme-deficient rat hepatocytes: translational control by a hepatic eIF2alpha kinase, the heme-regulated inhibitor
J. Pharmacol. Exp. Ther.
323
979-989
2007
Rattus norvegicus
Mueller, A.C.; Daya, S.
Acyclovir inhibits rat liver tryptophan-2,3-dioxygenase and induces a concomitant rise in brain serotonin and 5-hydroxyindole acetic acid levels
Metab. Brain Dis.
23
351-360
2008
Rattus norvegicus
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