Information on EC 1.13.11.11 - tryptophan 2,3-dioxygenase

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

EC NUMBER
COMMENTARY
1.13.11.11
-
RECOMMENDED NAME
GeneOntology No.
tryptophan 2,3-dioxygenase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
L-tryptophan + O2 = N-formyl-L-kynurenine
show the reaction diagram
-
-
-
-
L-tryptophan + O2 = N-formyl-L-kynurenine
show the reaction diagram
density functional theory calculations have been performed to elucidate the new reaction mechanism of oxidative cleavage of Trp
-
L-tryptophan + O2 = N-formyl-L-kynurenine
show the reaction diagram
substrate recognition and catalytic mechanism, overview
P20351
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
redox reaction
-
-
reduction
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
Metabolic pathways
-
tryptophan degradation I (via anthranilate)
-
tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde
-
tryptophan degradation XI (mammalian, via kynurenine)
-
Tryptophan metabolism
-
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].
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
EC 1.11.1.4
-
-
formerly
-
EC 1.13.1.12
-
-
formerly
-
IDO
P28776
-
INDO
P28776
-
indolamine 2,3-dioxygenase
-
-
-
-
indolamine 2,3-dioxygenase
-
-
indoleamine 2,3-dioxygenase
-
-
-
-
indoleamine 2,3-dioxygenase
-
-
indoleamine 2,3-dioxygenase
B3Y9H8
-
indoleamine 2,3-dioxygenase
-
-
indoleamine 2,3-dioxygenase
B3Y9H6
-
indoleamine 2,3-dioxygenase-2
-
-
indoleamine 2,3-dioxygenase-2
B3Y9H9
-
indoleamine 2,3-dioxygenase-2
-
-
indoleamine 2,3-dioxygenase-2
B1AC39
-
indoleamine 2,3-dioxygenase-2
B3Y9H7
-
indoleamine 2,3-dioxygenase-2
-
-
indoleamine 2,3-dioxygenase-like protein
B1AC39
-
L-tryptophan 2,3-dioxygenase
-
-
L-tryptophan pyrrolase
-
-
-
-
oxygenase, tryptophan 2,3-di-
-
-
-
-
proto-indoleamine 2,3-dioxygenase
-
-
proto-indoleamine 2,3-dioxygenase
B3Y9H9
-
proto-indoleamine 2,3-dioxygenase
-
-
proto-indoleamine 2,3-dioxygenase
B1AC39
-
proto-indoleamine 2,3-dioxygenase
B3Y9H7
-
proto-indoleamine 2,3-dioxygenase
-
-
superoxygenase
-
-
-
-
TDO
P48775
-
TDO
P48776
-
TDO
P21643
-
TDO2
P48775
-
TDO2
P48776
-
TDO2
P21643
-
TO
-
-
-
-
TRPO
-
-
-
-
Tryptamin 2,3-dioxygenase
-
-
-
-
tryptamine 2,3-dioxygenase
-
-
-
-
tryptophan 2,3-dioxygenase
-
-
tryptophan 2,3-dioxygenase
-
-
tryptophan 2,3-dioxygenase
-
-
tryptophan 2,3-dioxygenase
-
-
tryptophan 2,3-dioxygenase
-
three splicing variants
tryptophan 2,3-dioxygenase
-
-
tryptophan 2,3-dioxygenase
-
-
tryptophan 2,3-dioxygenase
-
-
tryptophan 2,3-dioxygenase
-
-
tryptophan 2,3-dioxygenase
Q8PDA8
-
tryptophan dioxygenase
-
-
tryptophan dioxygenase
-
-
tryptophan oxygenase
-
-
-
-
tryptophan oxygenase
-
-
tryptophan peroxidase
-
-
-
-
tryptophan pyrrolase
-
-
-
-
tryptophan-2,3-dioxygenase
-
-
tryptophanase
-
-
-
-
Vermilion protein
P20351
-
CAS REGISTRY NUMBER
COMMENTARY
9014-51-1
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
strain ATCC 19213
-
-
Manually annotated by BRENDA team
tryptophan 2,3-dioxygenase
-
-
Manually annotated by BRENDA team
definite classification as EC 1.13.11.11 based on protein sequence
SwissProt
Manually annotated by BRENDA team
Frog
-
-
-
Manually annotated by BRENDA team
definite classification as EC 1.13.11.11 based on protein sequence
SwissProt
Manually annotated by BRENDA team
definite classification as EC 1.13.11.42 based on protein sequence
SwissProt
Manually annotated by BRENDA team
indoleamine 2,3-dioxygenase
-
-
Manually annotated by BRENDA team
strain ML1, recombinantly expressed in Escherichia coli as a N-terminally His6-tagged protein
-
-
Manually annotated by BRENDA team
strain ML1, recombinantly expressed in Escherichia coli as a N-terminally His6-tagged protein
-
-
Manually annotated by BRENDA team
also another splice-variant detected, XM_001381868: predicted coding sequences from genomic sequences
SwissProt
Manually annotated by BRENDA team
XM_001381865: predicted coding sequences from genomic sequences
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
definite classification as EC 1.13.11.11 based on protein sequence
SwissProt
Manually annotated by BRENDA team
definite classification as EC 1.13.11.42 based on protein sequence
SwissProt
Manually annotated by BRENDA team
XM_001516116: predicted coding sequences from genomic sequences
SwissProt
Manually annotated by BRENDA team
XM_001516468, XM_001521552: predicted coding sequences from genomic sequences
SwissProt
Manually annotated by BRENDA team
indoleamine 2,3-dioxygenase
-
-
Manually annotated by BRENDA team
definite classification as EC 1.13.11.11 based on protein sequence
SwissProt
Manually annotated by BRENDA team
indoleamine 2,3-dioxygenase from small intestine; tryptophan 2,3-dioxygenase from liver
-
-
Manually annotated by BRENDA team
tryptophan 2,3-dioxygenase from liver
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
the kynurenine pathway is over-activated in Alzheimer's disease mice
metabolism
-
tryptophan 2,3-dioxygenase is an essential enzyme in the pathway of NAD biosynthesis
metabolism
P20351
tryptophan 2,3-dioxygenase catalyzes the oxidative cleavage of the indole ring of L-tryptophan to N-formylkynurenine in the kynurenine pathway
physiological function
-
TDO expression distinguishes stem cells from more differentiated cells among the granule cells of the adult mouse dentate gyrus. TDO is required at a late-stage of granule cell development, such as during axonal and dendritic growth, synaptogenesis and its maturation
metabolism
-
tryptophan 2,3 dioxygenase is the key regulatory enzyme of the kynurenine pathway
additional information
-
Xanthomonas campestris TDO shows an H-bond between T254 and the ammonium group of the substrate is present in the L-Trp-bound enzyme, but not in the D-Trp bound enzyme, molecular dynamics simulation studies. T254 controls the substrate stereoselectivity of the enzyme by modulating the H-bonding interaction between the NH3-group and epoxide oxygen of the ferryl/indole 2,3-epoxide intermediate of the enzyme, and regulating the dynamics of two active site loops, loop250-260 and loop117-130, critical for substrate-binding, O2 and L-trp both are bound in the active site
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1H-indole + H2O + O2
2,3-dihydro-1H-indole-2,3-diol
show the reaction diagram
-
-
-
-
-
5-fluoro-DL-tryptophan + O2
?
show the reaction diagram
Q8PDA8, -
-
-
-
?
5-fluoro-DL-tryptophan + O2
?
show the reaction diagram
-
-
-
-
?
5-fluoro-tryptophan + O2
?
show the reaction diagram
-
-
-
-
?
5-fluorotryptophan + O2
?
show the reaction diagram
-
-
-
-
?
5-hydroxytryptamine + O2
?
show the reaction diagram
-
-
-
-
?
5-methyl-DL-tryptophan + O2
?
show the reaction diagram
-
-
-
-
?
6-fluoro-DL-tryptophan + O2
?
show the reaction diagram
Q8PDA8, -
-
-
-
?
6-fluoro-DL-tryptophan + O2
?
show the reaction diagram
-
-
-
-
?
6-fluorotryptophan + O2
?
show the reaction diagram
-
-
-
-
?
6-methyl-DL-tryptophan + O2
?
show the reaction diagram
-
-
-
-
?
D-5-hydroxytryptophan + O2
?
show the reaction diagram
-
-
-
-
-
D-5-hydroxytryptophan + O2
?
show the reaction diagram
-
enzyme from lung
-
-
?
D-Trp + O2
N-formyl-D-kynurenine
show the reaction diagram
-
-
-
-
?
D-Trp + O2
N-formyl-D-kynurenine
show the reaction diagram
-
-
-
-
-
D-Trp + O2
N-formyl-D-kynurenine
show the reaction diagram
-
-
-
-
?
D-Trp + O2
N-formyl-D-kynurenine
show the reaction diagram
-
-
-
?
D-Trp + O2
N-formyl-D-kynurenine
show the reaction diagram
-
enzyme from brain
-
-
?
D-Trp + O2
N-formyl-D-kynurenine
show the reaction diagram
-
no activity with D-Trp
-
-
-
D-Trp + O2
N-formyl-D-kynurenine
show the reaction diagram
-
0.7% of the activity with L-Trp
-
-
?
D-Trp + O2
D-formylkynurenine
show the reaction diagram
P48775
-
-
-
?
D-tryptophan + O2
N-formyl-D-kynurenine
show the reaction diagram
-
-
-
-
ir
D-tryptophan + O2
N-formyl-D-kynurenine
show the reaction diagram
-
the initial deprotonation reaction of the indole NH group in hTDO is carried out by the evolutionarily conserved distal His. stereospecificity of hTDO is determined by the efficiency of the dioxygen chemistry
-
-
?
D-tryptophan + O2
N-formyl-D-kynurenine
show the reaction diagram
-
while L and D-tryptophan have similar affinities (Km values), the kcat is 10times lower for D-tryptophan
-
-
?
D-tryptophan + O2
N-formyl-D-kynurenine
show the reaction diagram
-
-
-
-
ir
DL-5-fluoro-methyltryptophan + O2
?
show the reaction diagram
-
30.6% of the activity with L-Trp
-
-
?
DL-5-fluoro-methyltryptophan + O2
?
show the reaction diagram
-
35% of the activity with L-Trp
-
-
?
DL-5-methyltryptophan + O2
?
show the reaction diagram
-
90% of the activity with L-Trp
-
-
?
DL-5-methyltryptophan + O2
?
show the reaction diagram
-
15.1% of the activity with L-Trp
-
-
?
DL-6-fluorotryptophan + O2
?
show the reaction diagram
-
-
-
-
?
DL-6-fluorotryptophan + O2
?
show the reaction diagram
-
90% of the activity with L-Trp
-
-
?
DL-6-methyltryptophan
?
show the reaction diagram
-
-
-
-
?
DL-6-methyltryptophan
?
show the reaction diagram
-
no activity
-
-
-
DL-6-methyltryptophan
?
show the reaction diagram
-
98% of the activity with L-Trp
-
-
?
DL-alpha-methyltryptophan + O2
alpha-methyl-N-formyl-DL-kynurenine
show the reaction diagram
-
9.0% of the activity with L-Trp
-
-
?
L-5-hydroxytryptophan + O2
?
show the reaction diagram
-
-
-
-
?
L-5-hydroxytryptophan + O2
?
show the reaction diagram
-
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
P48775
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
P21643
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
Frog
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
enzyme from liver is specific for L-Trp, the enzyme from brain is active with L-Trp and D-Trp, the enzyme from lung is active with L-Trp and D-5-hydroxytryptophan
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
superoxide anion is required for the initiation of the reaction and the maintenance of the catalytic cycle during the steady state
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
enzyme from liver is specific for
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
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
show the reaction diagram
-
absolutely specific for L-Trp
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
absolutely specific for L-Trp
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
indoleamine 2,3-dioxygenase has almost no detectable activity at or below 0.1 mM oxygen and maximum activity at about 1.15 mM
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
regulation of enzyme activity
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
lipopolysaccharide and muramyl tripeptide upregulate enzyme induction through a mechanism independent of interleukin 1alpha
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
interleukin-4 inhibits expression of the enzyme in monocytes
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
initial enzyme of tryptophan degradation pathway
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
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
show the reaction diagram
-
tryptophan-derived catabolites are responsible for inhibition of T cell and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
enzyme controls the physiological flux of Trp into both the serotonergic and kynureninic pathways
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
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
show the reaction diagram
P28776
induction by interferongamma
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
induction by interferongamma
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
the skin enzyme may play an important role in the initiation or suppression of rat hair growth
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
activity is increased in important biological processes, such as protection of the fetus from rejection during pregnancy and possibly T cell death in HIV-infected patients
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
first enzyme in the biosynthetic pathway of UV filters from Trp
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
regulatory control
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
key regulatory enzyme, though irreversible degradation, controls the flux of tryptophan through physiologically relevant pathways
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
P20351
during larval life the enzyme controls the level of potentially harmful free Trp in the hemolymph by converting it to kynurenine, and during adult development the enzyme catalyzes the first step of brown eye pigment biosynthesis
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
Trp degradation by the enzyme regulates lymphocyte proliferation
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
a dramatic and specific induction of the pulmonary enzyme by virus and lipopolysaccharide is mediated by interferon. The enzyme may play an important role in the inflammatory processes, immune responses, and/or the mode of action of interferon
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
influenza virus infection and tumor transplantation induce the enzyme
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
P48775
rate-limiting enzyme in the catabolism of tryptophan
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
enzyme contributes to tumor cell evasion of T cell-mediated rejection
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
expression of indoleamine 2,3-dioxygenase is an inducible feature of specific subsets of dendritic cells, and provides a potential mechanistic explanation for their T cell regulatory properties
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
IDO is the first enzyme in UV-filter pathway. UV-filter biosynthesis is active even in aged lenses
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
the enzyme inhibits tumor cell proliferation by tryptophan depletion. IDO-induced suppression of antitumoral immune response in both adenocarcinoma and squamous cell carcinoma
-
-
?
L-Trp + O2
N-formyl-L-kynurenine
show the reaction diagram
Q8PDA8, -
-
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
-
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
-
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
-
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
-
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
-
-
-
ir
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
P20351
-
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
-
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
-
-
-
ir
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
-
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
no activity with D-tryptophan
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
the enzyme is involved in tryptophan catabolism and in quinolinate biosynthesis
-
-
ir
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
the enzyme is involved in the catabolic pathway of L-tryptophan degradation, overview, D-tryptophan is no substrate
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
first step during biosynthesis of 3-hydroxyquinaldic acid
-
-
ir
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
indoleamine 2,3-dioxygenase is a rate-limiting enzyme in the L-tryptophan-kynurenine pathway. IFN-gamma-induced expression of IDO expression is inhibited only by JAK inhibitor I. Lipopolysaccharide-induced expression of indoleamine 2,3-dioxygenase is inhibited by LY294002 and SP600125 but not by JAK inhibitor I, SB203580, or U0126. LPS can induce the expression of indoleamine 2,3-dioxygenase via an IFN-gamma-independent mechanism and PI3 kinase and JNK in the LPS-induced pathway leading to IDO expression
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
rate-limiting enzyme in L-tryptophan catabolism and thus a key serotonergic determinant
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
tryptophan 2,3-dioxygenase is the only enzyme able to initiate L-tryptophan degradation through the kynurenine pathway
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
the initial deprotonation reaction of the indole NH group in hTDO is carried out by the evolutionarily conserved distal His. stereospecificity of hTDO is determined by the efficiency of the dioxygen chemistry
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
Q17P71
tryptophan indirectly activates TDO through promoting the production of reactive oxygen species
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
while L and D-tryptophan have similar affinities (Km values), the kcat is 10times lower for D-tryptophan
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
P20351
enzyme shows induced-fit mechanism to bind L-Trp, two conserved but flexible loops undergo conformational changes, converting the active site from an open conformation to a closed conformation, key residues involved in recognition and binding of the heme and the substrate, Molecular modeling and dynamics simulation, overview
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
-
-
-
ir
L-tryptophan + O2
N-formylkynurenine
show the reaction diagram
-
-
-
-
?
L-tryptophan + O2
N-formylkynurenine
show the reaction diagram
-
-
-
-
?
L-tryptophan + O2
N-formylkynurenine
show the reaction diagram
-
-
-
-
?
L-tryptophan + O2
N-formylkynurenine
show the reaction diagram
-
-
-
-
?
L-tryptophan + O2
N-formylkynurenine
show the reaction diagram
-
-
-
-
?
L-tryptophan + O2
N-formylkynurenine
show the reaction diagram
-
-
-
-
?
L-tryptophan + O2
N-formylkynurenine
show the reaction diagram
-
-
-
-
?
L-tryptophan + O2
N-formylkynurenine
show the reaction diagram
-
-
-
-
?
L-tryptophan + O2
N-formylkynurenine
show the reaction diagram
-
-
-
-
?
L-tryptophan + O2
N-formylkynurenine
show the reaction diagram
B3Y9H6, B3Y9H7
-
-
-
?
serotonin + O2
?
show the reaction diagram
-
-
-
-
?
serotonin + O2
?
show the reaction diagram
-
-
-
-
?
tryptamine + O2
?
show the reaction diagram
-
-
-
-
?
tryptamine + O2
?
show the reaction diagram
-
-
-
-
?
L-tryptophan + O2
N-formylkynurenine
show the reaction diagram
B3Y9H8, B3Y9H9
-
-
-
?
additional information
?
-
-
in the presence of guaiacol or potassium iodide the enzyme degrades H2O2
-
-
-
additional information
?
-
-
first and rate-limiting enzyme in tryptophan metabolism
-
-
-
additional information
?
-
-
first enzyme of the kynurenine pathway of tryptophan metabolism
-
-
-
additional information
?
-
-
in the placenta, inhibition of the enzyme leads to spontaneous abortion. By catabolizing extracellular tryptophan the enzyme inhibits local T cell proliferation thereby preventing placental rejection. This mechanism can also be active in suppressing inflammatory responses in the central neurvous system, where inflammation must be tightly regulated to prevent the loss of irreplaceable neurons. Local expression of the enzyme during inflammation is a self-protection mechanism which limits antigen-specific immune responses in the central nervous system
-
-
-
additional information
?
-
-
Langerhans cells possess an immunoregulatory function in promoting T cell tolerance by production of IDO
-
-
-
additional information
?
-
P48775
the oxidative metabolism of melatonin is due, in presence of H2O2, to the activities of both myeloperoxidase, EC 1.11.1.7 and indolemanine 2,3-dioxygenase
-
-
-
additional information
?
-
Q8PDA8, -
no activity with D-Trp and indolepropionic acid
-
-
-
additional information
?
-
-
no activity with tryptophanol, indole-3-propionic acid, tryptamine, N-methyl-Trp
-
-
-
additional information
?
-
-
TioF is completely inactive towards tryptamine, 5-hydroxy-L-Trp, and indole propionic acid
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
D-tryptophan + O2
N-formyl-D-kynurenine
show the reaction diagram
-
while L and D-tryptophan have similar affinities (Km values), the kcat is 10times lower for D-tryptophan
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
regulation of enzyme activity
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
lipopolysaccharide and muramyl tripeptide upregulate enzyme induction through a mechanism independent of interleukin 1alpha
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
interleukin-4 inhibits expression of the enzyme in monocytes
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
initial enzyme of tryptophan degradation pathway
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
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
show the reaction diagram
-
tryptophan-derived catabolites are responsible for inhibition of T cell and natural killer cell proliferation induced by indoleamine 2,3-dioxygenase
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
enzyme controls the physiological flux of Trp into both the serotonergic and kynureninic pathways
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
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
show the reaction diagram
P28776
induction by interferongamma
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
induction by interferongamma
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
the skin enzyme may play an important role in the initiation or suppression of rat hair growth
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
activity is increased in important biological processes, such as protection of the fetus from rejection during pregnancy and possibly T cell death in HIV-infected patients
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
first enzyme in the biosynthetic pathway of UV filters from Trp
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
regulatory control
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
key regulatory enzyme, though irreversible degradation, controls the flux of tryptophan through physiologically relevant pathways
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
P20351
during larval life the enzyme controls the level of potentially harmful free Trp in the hemolymph by converting it to kynurenine, and during adult development the enzyme catalyzes the first step of brown eye pigment biosynthesis
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
Trp degradation by the enzyme regulates lymphocyte proliferation
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
a dramatic and specific induction of the pulmonary enzyme by virus and lipopolysaccharide is mediated by interferon. The enzyme may play an important role in the inflammatory processes, immune responses, and/or the mode of action of interferon
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
influenza virus infection and tumor transplantation induce the enzyme
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
P48775
rate-limiting enzyme in the catabolism of tryptophan
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
enzyme contributes to tumor cell evasion of T cell-mediated rejection
-
-
-
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
expression of indoleamine 2,3-dioxygenase is an inducible feature of specific subsets of dendritic cells, and provides a potential mechanistic explanation for their T cell regulatory properties
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
IDO is the first enzyme in UV-filter pathway. UV-filter biosynthesis is active even in aged lenses
-
-
?
L-Trp + O2
L-formylkynurenine
show the reaction diagram
-
the enzyme inhibits tumor cell proliferation by tryptophan depletion. IDO-induced suppression of antitumoral immune response in both adenocarcinoma and squamous cell carcinoma
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
-
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
P20351
-
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
-
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
-
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
the enzyme is involved in tryptophan catabolism and in quinolinate biosynthesis
-
-
ir
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
the enzyme is involved in the catabolic pathway of L-tryptophan degradation, overview
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
first step during biosynthesis of 3-hydroxyquinaldic acid
-
-
ir
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
indoleamine 2,3-dioxygenase is a rate-limiting enzyme in the L-tryptophan-kynurenine pathway. IFN-gamma-induced expression of IDO expression is inhibited only by JAK inhibitor I. Lipopolysaccharide-induced expression of indoleamine 2,3-dioxygenase is inhibited by LY294002 and SP600125 but not by JAK inhibitor I, SB203580, or U0126. LPS can induce the expression of indoleamine 2,3-dioxygenase via an IFN-gamma-independent mechanism and PI3 kinase and JNK in the LPS-induced pathway leading to IDO expression
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
rate-limiting enzyme in L-tryptophan catabolism and thus a key serotonergic determinant
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
tryptophan 2,3-dioxygenase is the only enzyme able to initiate L-tryptophan degradation through the kynurenine pathway
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
-
while L and D-tryptophan have similar affinities (Km values), the kcat is 10times lower for D-tryptophan
-
-
?
additional information
?
-
-
first and rate-limiting enzyme in tryptophan metabolism
-
-
-
additional information
?
-
-
first enzyme of the kynurenine pathway of tryptophan metabolism
-
-
-
additional information
?
-
-
in the placenta, inhibition of the enzyme leads to spontaneous abortion. By catabolizing extracellular tryptophan the enzyme inhibits local T cell proliferation thereby preventing placental rejection. This mechanism can also be active in suppressing inflammatory responses in the central neurvous system, where inflammation must be tightly regulated to prevent the loss of irreplaceable neurons. Local expression of the enzyme during inflammation is a self-protection mechanism which limits antigen-specific immune responses in the central nervous system
-
-
-
additional information
?
-
-
Langerhans cells possess an immunoregulatory function in promoting T cell tolerance by production of IDO
-
-
-
additional information
?
-
P48775
the oxidative metabolism of melatonin is due, in presence of H2O2, to the activities of both myeloperoxidase, EC 1.11.1.7 and indolemanine 2,3-dioxygenase
-
-
-
COFACTOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
heme
-
enzyme contains heme; the already active reduced holoenzyme does not require haematin for activity, the heme-free predominant apoenzyme does
heme
-
enzyme contains heme; the already active reduced holoenzyme does not require haematin for activity, the heme-free predominant apoenzyme does
heme
-
enzyme contains heme
heme
-
enzyme contains two heme moieties
heme
P21643
enzyme contains 2 protoheme IV per molecule
heme
-
the prosthetic group is tightly bound to the enzyme
heme
-
contains 1 mol or more of heme per mol of enzyme
heme
-
the ferric form of the enzyme shows magnetic CD spectra ascribable to a high spin protohemoprotein at neutral pH
heme
-
the ferric form of the enzyme shows magnetic CD spectra ascribable to a mixture of low spin and high spin protohemoprotein at neutral pH
heme
-
the ferric form of the enzyme shows magnetic CD spectra ascribable to a high spin protohemoprotein at neutral pH
heme
-
the environmental structure of the active-site heme pocket is similar but the size is considerably larger than that of myoglobin
heme
-
studies of the heme coordination structure
heme
-
0.8 mol of protoheme IX per mol of enzyme; the native ferric form of the enzyme binds to the superoxide anion to form the oxygenated enzyme
heme
-
0.8 mol of protoheme IX per mol of enzyme
heme
-
characterization of the heme environment, strong proximal Fe-His bond and strond H-bonding and/or steric interactions between L-Trp and dioxygen in the distal pocket are likely crucial for the enzymatic activity of the recombinant enzyme
heme
-
1 mol of heme per mol of monomer
heme
-
2 mol of heme per tetramer
heme
-
2 mol of heme per tetramer
heme
-
contains protohematin IX as a prosthetic group
heme
-
1.12 mol of heme per mol of enzyme
heme
P48776
2 molecules of protoheme IV per tetramer
heme
-
hemoprotein. The use of ALA, the biosynthetic precursor of protoporphyrin IX, coupled with metal-affinity chromatography and size exclusion chromatography produces 6His-IDP with a protein to heme ratio of 1:2.2
heme
-
Ag-HisTDO is purified in its heme-ferric form. The prosthetic group can be fully converted into the heme-ferrous form by treatment with sodium dithionite
heme
-
TDO is regulated by heme, its prosthetic moiety, as its expression and function are significantly reduced after acute hepatic heme depletion
heme
P20351
DmTDO contains two major insertion sequences: one forms part of the heme-binding site and the other forms a large portion of the small domain, bindig structure, overview
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Cd2+
-
0.007-0.1 mM, maximal stimulation at 0.007 mM
copper
-
enzyme contains 2 copper moieties
copper
-
ratio of copper to heme is less than 0.03
copper
-
only trace amounts of copper
copper
-
contains 2 gatom of copper per mol of enzyme
copper
-
contains copper in significant quantity
copper
-
0.33 mol per mol of enzyme
Fe2+
-
the enzyme has a functional heme group
Fe2+
-
heme-containing enzyme
Fe2+
-
required, hydrogen peroxide-triggered enzyme reactivation from the resting ferric oxidation state to the catalytically active ferrous form, modeling, overviews
Fe2+
P20351
heme-scontaining enzyme
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(E)-6-fluoro-3-[2-(3-pyridyl)vinyl]-1H-indole
-
-
1-L-methyltryptophan
-
-
1-methyl-D-tryptophan
B1AC39
-
1-methyl-DL-Trp
-
-
1-Methyltryptophan
-
competitive
1-Methyltryptophan
-
2 mM, 70% inhibition; competitive
2-methylindole
-
-
3-hydroxyanthranilic acid
-
-
3-hydroxykynurenine
-
0.1 mM, weak inhibition amounting to about 30%
3-hydroxykynurenine
-
0.1 mM, 89.8% inhibition
3-methyl-8-(4,4,4-trifluorobutoxy)-5H-indeno[1,2-c]pyridazin-5-one
-
31% inhibition at 0.025 mM
3-methyl-8-[(3-methylbenzyl)oxy]-5H-indeno[1,2-c]pyridazin-5-one
-
66% inhibition at 0.025 mM
4-Hydroxypyrazole
-
-
5-hydroxy-L-Trp
-
-
5-hydroxyindole acetic acid
-
1 mM, 61.5% inhibition
5-hydroxytryptamine
-
1 mM, 82.3% inhibition
5-hydroxytryptophan
-
1 mM, 78.6% inhibition
8-(4,4,4-trifluorobutoxy)-3-[3-(trifluoromethyl)phenyl]-5H-indeno[1,2-c]pyridazin-5-one
-
20% inhibition at 0.025 mM
8-(benzyloxy)-3-[3-(trifluoromethyl)phenyl]-5H-indeno[1,2-c]pyridazin-5-one
-
-
8-methoxy-3-[3-(trifluoromethyl)phenyl]-5H-indeno[1,2-c]pyridazin-5-one
-
18% inhibition at 0.025 mM
8-[(3-chlorobenzyl)oxy]-3-methyl-5H-indeno[1,2-c]pyridazin-5-one
-
19% inhibition at 0.025 mM
acetaminophen
-
no affect on holoenzyme, significant inhibition of apoenzyme, changes in brain serotonin levels due to inhibition of hepatic tryptophan 2,3-dioxygenase
Bathocuproinesulfonate
-
competitive with respect to L-Trp and noncompetitive with respect to O2
Cd2+
-
0.5-1.0 mM, non-competitive
Cinnabarinic acid
-
-
CN-
-
5 mM, 98% inhibition
CN-
-
0.4 mM, 86% inhibition
CN-
-
9.6 mM, 50% inhibition
CO
-
20% with 80% air, 78% inhibition
Cu2+
-
0.005 mM, 50% inhibition
D-Trp
-
no inhibition
diethyldithiocarbamate
-
5 mM, markedly enhances activity
DL-5-fluorotryptophan
-
-
DL-5-hydroxytryptophan
-
1 mM, 55% inhibition
DL-5-Methyltryptophan
-
-
DL-alpha-methyltryptophan
-
-
H2O2
-
inactivated by H2O formed by ascorbic acid in presence of methylen blue
H2O2
-
at high concentrations
hydroxylamine
-
-
Indole
-
1 mM, 44% inhibition
Indolepropionic acid
-
1 mM, 31% inhibition
K3Fe(CN)6
-
1 mM, complete inhibition
Kynurenic acid
-
0.1 mM, 57.2% inhibition. 1 mM, 99.4% inhibition
L-kynurenine
-
0.1 mM, 17.7% inhibition. 1 mM, 93.6% inhibition
N1-acetyl-N2-formyl-5-methoxykynurenine
-
-
N3-
-
5 mM, 5% inhibition
N3-
-
2 mM, 22% inhibition
NADH
-
0.1 mM, 51.3% inhibition
NH2OH
-
2 mM, 54% inhibition
norharman
-
2 mM, 98% inhibition, uncompetitive
O2
-
inhibition of mutant forms H55A and H55S at high concentrations
potassium cyanide
-
-
Superoxide dismutase
-
-
-
tryptamine
-
1 mM, 23% inhibition
tryptamine
-
-
xanthurenic acid
-
0.1 mM, 50.6% inhibition. 1 mM, 96.2% inhibition
L-tryptophan
-
substrate inhibition (above 0.05 mM)
additional information
-
no inhibition by D-5-hydroxytryptophan
-
additional information
-
inhibition of indoleamine 2,3-dioxygenase may be developed as an anticancer immunotherapeutic strategy
-
additional information
-
catabolite repression of the pathway by glucose and glutamate, arginine does not cause repression, no inhibition by D-tryptophan
-
additional information
-
synthesis and inhibition study of tryptophan 2,3-dioxygenase with 3,8-substituted 5H-indeno[1,2-c]pyridazin-5-one derivatives, overview. No inhibition by 7b
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
4-Hydroxypyrazole
-
below 0.1 mM, activation
alpha-methyl-DL-tryptophan
-
can activate the enzyme when lower concentrations of L-Trp are used
ascorbic acid
-
native and recombinant enzyme require methylene blue and ascorbic acid for activity
ascorbic acid
-
tryptophan 2,3-dioxygenase: maximal activity at 10 mM ascorbate
ascorbic acid
-
the ferric enzyme is incapable of catalyzing the reaction but is reduced to an active ferrous form by the addition of ascorbic acid and L-Trp in presence of O2
ascorbic acid
-
9.2 mM required for half-maximal activity
ascorbic acid
-
activates
Cys
-
can reduce the inactive ferric form of the enzyme to the active ferrous form
DTT
-
can reduce the inactive ferric form of the enzyme to the active ferrous form
ethylhydroperoxide
-
can reduce the inactive ferric form of the enzyme to the active ferrous form
GSH
-
can reduce the inactive ferric form of the enzyme to the active ferrous form
H2O2
-
can reduce the inactive ferric form of the enzyme to the active ferrous form
H2O2
-
hydrogen peroxide-triggered enzyme reactivation from the resting ferric oxidation state to the catalytically active ferrous form, modeling, overview
methylene blue
-
native and recombinant enzyme require methylene blue and ascorbic acid for activity
methylene blue
-
no activity without, half-maximal activity at 0.002 mM
superoxide
-
the enzyme is inactive unless superoxide anion is present, the native ferric form of the enzyme binds to the superoxide anion to form the oxygenated enzyme
methylhydroperoxide
-
can reduce the inactive ferric form of the enzyme to the active ferrous form
additional information
-
the enzyme can be activated through different pathways either by superoxide anion or by an electron donor-methylene blue system where the dye is acting as an electron mediator from the donor to the ferric dioxygenase
-
additional information
-
aerobically photoactivation as well as anaerobically by light of wavelength less than 360 nm, the substrate, L-Trp must be present for photoactivation to proceed, 6-fluorotryptophan can mediate photoactivation
-
additional information
-
kynurenine induces both tryptophan oxygenase and kynureninase of the catabolic pathway of L-tryptophan degradation
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.1
-
5-fluoro-DL-tryptophan
-
O2 not present at a saturating level
0.183
-
5-fluoro-DL-tryptophan
-
H55S mutant enzyme, O2 not present at a saturating level
0.194
-
5-fluoro-DL-tryptophan
-
H55A mutant enzyme, O2 not present at a saturating level
100
-
5-fluoro-DL-tryptophan
-
25C, pH 7.5, wild-type enzyme
0.36
-
5-fluoro-tryptophan
-
-
0.6
-
5-hydroxy-D-tryptophan
-
24C
0.02
-
5-hydroxy-L-tryptophan
-
24C
0.44
-
5-hydroxy-L-tryptophan
-
recombinant enzyme
0.357
-
5-methyl-DL-tryptophan
-
O2 not present at a saturating level
0.395
-
5-methyl-DL-tryptophan
-
H55A mutant enzyme, O2 not present at a saturating level
1.302
-
5-methyl-DL-tryptophan
-
H55S mutant enzyme
0.186
-
6-fluoro-DL-tryptophan
-
O2 not present at a saturating level
0.195
-
6-fluoro-DL-tryptophan
-
H55A mutant enzyme, O2 not present at a saturating level
0.546
-
6-fluoro-DL-tryptophan
-
H55S mutant enzyme, O2 not present at a saturating level
186
-
6-fluoro-DL-tryptophan
-
25C, pH 7.5, wild-type enzyme
0.386
-
6-methyl-DL-tryptophan
-
H55A mutant enzyme, O2 not present at a saturating level
0.975
-
6-methyl-DL-tryptophan
-
O2 not present at a saturating level
1.98
-
6-methyl-DL-tryptophan
-
H55S mutant enzyme, O2 not present at a saturating level
5
-
D-Trp
-
recombinant enzyme
5.2
-
D-Trp
-
-
0.18
-
D-tryptophan
-
pH 7.0
0.44
-
D-tryptophan
-
-
16
-
D-tryptophan
-
pH and temperature not specified in the publication
30.27
-
Indole
-
-
0.02
-
L-Trp
-
recombinant enzyme
0.0246
-
L-Trp
-
-
0.043
-
L-Trp
-
-
0.045
-
L-Trp
-
24C
0.114
-
L-Trp
-
25C, pH 7.5, wild-type enzyme
0.25
-
L-Trp
-
pH 8.0
0.3
-
L-Trp
-
pH 7.0
7.7
-
L-Trp
-
activated by 0.033 mM Cd2+
133
-
L-Trp
-
25C, pH 7.5, mutant enzyme H55A
0.0063
-
L-tryptophan
B3Y9H8, B3Y9H9
-
0.0191
-
L-tryptophan
-
-
0.0537
-
L-tryptophan
B3Y9H6, B3Y9H7
-
0.0825
-
L-tryptophan
-
pH 8.0, normal atmospheric conditions
0.114
-
L-tryptophan
-
-
0.114
-
L-tryptophan
-
O2 not present at a saturating level
0.114
-
L-tryptophan
-
pH and temperature not specified in the publication
0.133
-
L-tryptophan
-
H55A mutant enzyme, O2 not present at a saturating level
0.18
-
L-tryptophan
-
pH 7.0, normal atmospheric conditions
0.19
-
L-tryptophan
-
pH 7.0
0.197
-
L-tryptophan
-
H55S mutant enzyme, O2 not present at a saturating level
0.222
-
L-tryptophan
-
-
0.488
-
L-tryptophan
-
H76A mutant enzyme, pH 8.0, normal atmospheric conditions
0.6
-
L-tryptophan
-
-
0.65
-
L-tryptophan
-
-
1.29
-
L-tryptophan
-
Y42F mutant enzyme, pH 8.0, normal atmospheric conditions
11.7
-
L-tryptophan
-
-
28.2
-
L-tryptophan
-
-
54.1
-
L-tryptophan
-
-
60.7
-
L-tryptophan
B3Y9H8, B3Y9H9
-
62.4
-
L-tryptophan
B3Y9H6, B3Y9H7
-
0.037
-
O2
-
pH 8.0
0.038
-
O2
-
pH 7.0
2.8
-
O2
-
indoleamine 2,3-dioxygenase
45.7
-
O2
-
H55A mutant enzyme
99
-
O2
-
H55S mutant enzyme
119
-
O2
-
25C, pH 7.5, wild-type enzyme
0.1
-
serotonin
-
24C
2.56
-
serotonin
-
-
0.075
-
tryptamine
-
24C
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.68
-
5-fluoro-DL-tryptophan
-
H55A mutant enzyme, O2 not present at a saturating level
0.8
-
5-fluoro-DL-tryptophan
-
H55S mutant enzyme, O2 not present at a saturating level
2.4
-
5-fluoro-DL-tryptophan
-
25C, pH 7.5, wild-type enzyme
2.4
-
5-fluoro-DL-tryptophan
-
O2 not present at a saturating level
0.18
-
5-fluoro-tryptophan
-
-
0.00967
-
5-hydroxy-D-tryptophan
-
24C
0.0433
-
5-hydroxy-L-tryptophan
-
24C
0.065
-
5-hydroxy-L-tryptophan
-
-
0.4
-
5-methyl-DL-tryptophan
-
H55A mutant enzyme, O2 not present at a saturating level
1.45
-
5-methyl-DL-tryptophan
-
H55S mutant enzyme, O2 not present at a saturating level
3.59
-
5-methyl-DL-tryptophan
-
O2 not present at a saturating level
3.78
-
6-fluoro-DL-tryptophan
-
H55A mutant enzyme, O2 not present at a saturating level
3.8
-
6-fluoro-DL-tryptophan
-
H55S mutant enzyme, O2 not present at a saturating level
37.3
-
6-fluoro-DL-tryptophan
-
25C, pH 7.5, wild-type enzyme
37.3
-
6-fluoro-DL-tryptophan
-
O2 not present at a saturating level
1.65
-
6-methyl-DL-tryptophan
-
H55A mutant enzyme, O2 not present at a saturating level
4.66
-
6-methyl-DL-tryptophan
-
H55S mutant enzyme, O2 not present at a saturating level
41
-
6-methyl-DL-tryptophan
-
O2 not present at a saturating level
2.07
-
D-Trp
-
-
0.0068
-
D-tryptophan
-
-
0.2
-
D-tryptophan
-
pH 7.0
0.248
-
Indole
-
-
1.55
-
L-Trp
-
-
2.86
-
L-Trp
-
25C, pH 7.5, mutant enzyme H55A
3
6
L-Trp
-
25C, pH 7.5, mutant enzyme H55A
19.5
-
L-Trp
-
25C, pH 7.5, wild-type enzyme
0.04
-
L-tryptophan
-
H76A mutant enzyme, pH 8.0, normal atmospheric conditions
0.045
-
L-tryptophan
-
-
0.6
-
L-tryptophan
-
pH 7.0, normal atmospheric conditions
0.9
-
L-tryptophan
B3Y9H8, B3Y9H9
-
1.4
-
L-tryptophan
-
-
1.8
-
L-tryptophan
-
-
2.03
-
L-tryptophan
-
-
2.1
-
L-tryptophan
-
pH 7.0
2.2
-
L-tryptophan
-
-
2.6
-
L-tryptophan
-
H55S mutant enzyme, O2 not present at a saturating level
2.6
-
L-tryptophan
-
-
2.86
-
L-tryptophan
-
H55A mutant enzyme, O2 not present at a saturating level
2.9
-
L-tryptophan
B3Y9H6, B3Y9H7
-
3.04
-
L-tryptophan
-
Y42F mutant enzyme, pH 8.0, normal atmospheric conditions
3.86
-
L-tryptophan
-
H55A mutant enzyme
4.3
-
L-tryptophan
B3Y9H6, B3Y9H7
-
6.12
-
L-tryptophan
-
pH 8.0, normal atmospheric conditions
7.88
-
L-tryptophan
-
H55S mutant enzyme
16.8
-
L-tryptophan
-
-
19
-
L-tryptophan
B3Y9H8, B3Y9H9
-
19.5
-
L-tryptophan
-
O2 not present at a saturating level
35.4
-
O2
-
25C, pH 7.5, wild-type enzyme
0.00283
-
serotonin
-
24C
0.028
-
serotonin
-
-
0.00483
-
tryptamine
-
24C
35.4
-
L-tryptophan
-
-
additional information
-
additional information
-
2070 per min, formylkynurenine formed
-
additional information
-
additional information
-
420 per min, formylkynurenine formed
-
additional information
-
additional information
-
-
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.000051
-
(E)-6-fluoro-3-[2-(3-pyridyl)vinyl]-1H-indole
-
-
0.023
-
1-methyl-DL-Trp
-
-
0.068
-
1-Methyltryptophan
-
-
0.158
-
2-methylindole
-
-
0.03
-
4-Hydroxypyrazole
-
-
0.072
-
5-hydroxy-L-Trp
-
-
0.031
-
Bathocuproinesulfonate
-
-
0.33
-
DL-4-fluorotryptophan
-
-
1
-
DL-4-fluorotryptophan
-
-
0.28
-
DL-4-methyltryptophan
-
-
0.67
-
DL-4-methyltryptophan
-
-
0.12
-
DL-5-fluorotryptophan
-
-
0.39
-
DL-5-fluorotryptophan
-
-
0.19
-
DL-5-Methyltryptophan
-
-
0.55
-
DL-5-Methyltryptophan
-
-
0.14
-
Indole
-
-
0.08
-
Indolepropionic acid
-
-
0.21
-
Indolepropionic acid
-
-
0.001
-
L-5-hydroxytryptophan
-
-
0.01
-
L-5-hydroxytryptophan
-
-
0.17
-
L-tryptophan
-
-
0.176
-
norharman
-
-
0.48
-
O2
-
H55S mutant enzyme
1.38
-
O2
-
H55A mutant enzyme
0.1
-
tryptamine
-
-
0.255
-
tryptamine
-
-
1.8
-
tryptamine
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
0.38
-
-
-
2.58
-
-
-
2.67
-
-
-
12.5
-
-
cells grown on L-alanine
15.6
-
-
cells grown on L-asparagine
22.7
-
-
cells grown on L-tryptophan
23.5
-
-
cells grown on L-arginine
additional information
-
-
influence of some methodological factors on measurement of tryptophan oxygenase activities in crude homogenates of rat liver
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
-
additional information
-
-
poor activity in cells grown on arginine and on glucose, also in presence of L-tryptophan
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.5
-
-
-
7
-
-
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6
9
-
pH 6.0: about 45% of maximal activity, pH 9.0: about 40% of maximal activity
6.5
9
-
pH 6.5: about 50% of maximal activity, pH 9.0: about 70% of maximal activity
7
9.5
-
pH 7.0: about 40% of maximal activity, pH 9.5: about 50% of maximal activity
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
-
-
assay at
pI VALUE
pI VALUE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.4
-
-
calculated from sequence
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
detectable immunohistochemically from day 6
Manually annotated by BRENDA team
-
indoleamine 2,3-dioxygenase
Manually annotated by BRENDA team
-
activity with D-Trp and L-Trp
Manually annotated by BRENDA team
-
Alzheimer's disease brain
Manually annotated by BRENDA team
-
enzyme activity in triple transgenic Alzheimer's disease mice. Expression of TDO mRNA is significantly increased in the cerebellum of Alzheimer's disease mouse brain
Manually annotated by BRENDA team
-
cells grown in a medium containing L-tryptophan as the sole carbon, nitrogen, and energy source
Manually annotated by BRENDA team
-
CD123+/CCR6+ dendritic cells do not constitutively express indoleamine 2,3-dioxygenase, and, even if they express the enzyme after interferon-gamma treatment, they possess only limited T-cell regulatory function
Manually annotated by BRENDA team
-
the expression of the enzyme is selectively induced in specific splenic dendritic cell subsets when mice are exposed to the synthetic immunomodulatory reagent CTLA4-Ig
Manually annotated by BRENDA team
-
derived from bone marrow
Manually annotated by BRENDA team
-
despite suppression by progesterone, indoleamine 2,3-dioxygenase expression in endometrial stromal cells may increase during decidualization due to stimulation by interferon-gamma secreted by infiltrating leukocytes
Manually annotated by BRENDA team
-
of uterine endometrium and cervix
Manually annotated by BRENDA team
-
diploid fibroblast cells FS-4
Manually annotated by BRENDA team
-
mature granule cells of the adult mouse dentate gyrus
Manually annotated by BRENDA team
-
primary hepatocyte
Manually annotated by BRENDA team
-
expression of TDO mRNA is significantly increased in the hippocampus of Alzheimer's disease patient brain. TDO co-localizes with quinolinic acid, neurofibrillary tangles-tau and amyloid deposits in the hippocampus of Alzheimer's disease patient brain
Manually annotated by BRENDA team
B1AC39
predominantly expressed
Manually annotated by BRENDA team
-
Langerhans cells possess an immunoregulatory function in promoting T cell tolerance by production of IDO
Manually annotated by BRENDA team
-
the enzyme is localized in the anterior cortex of the lens with little or no activity in the posterior cortex or nucleus
Manually annotated by BRENDA team
-
enzyme activity is detected in all lenses ranging from 26 to 80 years and there are no clear relationship of IDO activity with age
Manually annotated by BRENDA team
-
tryptophan 2,3-dioxygenase
Manually annotated by BRENDA team
-
liver enzyme is specific for L-Trp
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
-
indoleamine 2,3-dioxygenase
Manually annotated by BRENDA team
-
activity with L-Trp and D-5-hydroxytryptophan
Manually annotated by BRENDA team
-
enzyme is induced in monocyte-derived macrophages treated with human recombinant interferon-beta or interferon gamma
Manually annotated by BRENDA team
-
in the villous stroma and in the fetal membrane
Manually annotated by BRENDA team
-
indoleamine 2,3-dioxygenase
Manually annotated by BRENDA team
-
premetamorphic stage
Manually annotated by BRENDA team
additional information
-
placental enzyme is not expressed in the maternal facing brush border membrane of syncytiotrophoblast
Manually annotated by BRENDA team
additional information
-
cell in the peritumoral infiltrate of the stroma
Manually annotated by BRENDA team
additional information
-
quantitative real-time RT PCR enzyme expression analysis in brain sectiions
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
enzyme is confined to cytosol
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Ralstonia metallidurans (strain CH34 / ATCC 43123 / DSM 2839)
Shewanella oneidensis (strain MR-1)
Shewanella oneidensis (strain MR-1)
Xanthomonas campestris pv. campestris (strain ATCC 33913 / NCPPB 528 / LMG 568)
Xanthomonas campestris pv. campestris (strain ATCC 33913 / NCPPB 528 / LMG 568)
Xanthomonas campestris pv. campestris (strain ATCC 33913 / NCPPB 528 / LMG 568)
Xanthomonas campestris pv. campestris (strain ATCC 33913 / NCPPB 528 / LMG 568)
Xanthomonas campestris pv. campestris (strain ATCC 33913 / NCPPB 528 / LMG 568)
Xanthomonas campestris pv. campestris (strain ATCC 33913 / NCPPB 528 / LMG 568)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
16000
-
-
enzyme from skin, gel filtration
42000
-
-
sedimentation velocity experiments
45000
-
-
SDS-PAGE
54000
-
-
gel filtration
105000
-
-
enzyme from intestine, gel filtration
118000
-
-
high speed equilibrium sedimentation
120000
-
-
gel filtration
120000
-
-
about 120000 Da in prokaryotes
122000
-
-
gel filtration, sucrose density gradient centrifugation, equilibrium sedimentation
123000
-
-
low speed equilibrium sedimentation
160000
180000
-
gel filtration, sucrose density gradient centrifugation
167000
-
-
gel filtration, sucrose density gradient centrifugation, equilibrium sedimentation
167000
-
-
-
167000
-
-
high speed equilibrium sedimentation
additional information
-
P48775
sequence of the human TDO2 gene, presence of a glucocorticoid response-like element composed of a GTT repeat and an intronic CCCCT repeat
additional information
-
-
primary structure deduced from sequence of cDNA
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
P28776
x * 45639, calculation from nucleotide sequence
?
-
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
?
-
x * 44800, calculated from sequence
?
Q17P71
x * 42000, SDS-PAGE
?
-
x * 47900, SDS-PAGE
homotetramer
-
native-PAGE
homotetramer
-
x-ray crystallography
monomer
-
1 * 40000, SDS-PAGE; 1 * 41000, sedimentation velocity experiments in presence of 6 M guanidine HCl
monomer
-
1 * 45000
tetramer
-
4 * 31000, SDS-PAGE
tetramer
P21643
; 4 * 47796, calculation from nucleotide sequence
tetramer
-
4 * 27000, SDS-PAGE
tetramer
-
alpha2beta2, 2 * 43000 + 2 * 43000, SDS-PAGE
tetramer
-
-
tetramer
-
gel filtration
tetramer
P20351
the enzme consists of an N-terminal segment, a large domain and a small domain, and assumes a tetrameric architecture. DmTDO contains two major insertion sequences: one forms part of the heme-binding site and the other forms a large portion of the small domain
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
glycoprotein
-
1.2 galactose, 2.6 mannose, 5.2 N-acetylglucosamine and 0.8 sialic acid residues per mol of enzyme; contains approximately 5% carbohydrate per weight
glycoprotein
-
contains approximately 5% carbohydrate per weight
glycoprotein
-
1.2 galactose, 2.6 mannose, 5.2 N-acetylglucosamine and 0.8 sialic acid residues per mol of enzyme; 5.4% carbohydrate
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
vapour-diffusion method, structure of the enzyme with cofactor heme bound in the active site, 2.4 A resolution
-
purified His6-tagged recombinant enzyme in complex with heme, hanging drop vapor diffusion method, mixing of 20 mg/ml protein in 20 mM Tris, pH 8.0, and 200 mM NaCl, with reservoir solution containing 0.1 M HEPES, pH 7.0, and 1.1 M sodium malonate, at equal volumes, 20C, X-ray diffraction structure determination and analysis at 2.7 A resolution
P20351
hanging drop vapor diffusion, 18C, PEG 1000
-
sitting-drop vapor diffusion method, crystal structures at up to 1.6-A resolution of the active, reduced (Fe(II)) enzyme in a binary complex with the substrate L-Trp or 6-fluoro-Trp
-
pH STABILITY
pH STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
4
-
-
4C, 6 h, 52% loss of activity
5
-
-
4C, 6 h, 7% loss of activity
6
-
-
4C, no loss of activity after 6 h
6.5
-
-
most stable at
7
-
-
4C, 6 h, 15% loss of activity
8
-
-
4C, 6 h, 55% loss of activity
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
55
-
-
pH 6.0, 5 min, 43% loss of dioxygenase activity on L-Trp and D-Trp, 55% loss ofter 10 min, 70% loss ofter 20 min
70
-
-
30 min, stable in presence of 5 mM L-Trp
75
-
-
30 min, about 5% loss of activity in presence of 5 mM L-Trp
80
-
-
30 min, about 35% loss of activity in presence of 5 mM L-Trp
85
-
-
30 min, complete loss of activity in presence of 5 mM L-Trp
additional information
-
-
L-Trp stabilizes against heat inactivation
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
guanidine hydrochloride, 30C, 30 min, about 15% loss of activity at 0.5 M, about 30% loss of activity at 1 mM, about 60% loss of activity at 2 M, complete loss of activity at 3 mM
-
urea, 30C, 30 min, stable at 2.5 M, about 30% loss of activity at 5.0 M, about 60% loss of activity at 7.5 M
-
freezing and thawing causes 66% loss of activity
-
unstable in purified state, if the substrate is omitted during the last step, the activity is lost entirely
-
enzyme is most stable in presence of L-Trp or alpha-methyl-DL-tryptophan, and in absence of oxygen
-
OXIDATION STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
most stable in absence of oxygen
-
395489
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
pH 7.0, anaerobically stored in 0.1 M potassium phosphate buffer containing L-Trp, quite stable
-
5C, 48 h, 23% loss of activity
-
-70C, stable for at least 2 months
-
0C, under anaerobic conditions in presence of tryptophan, stable for several days
-
-9C, pH 7, stable in 0.1 M phosphate buffer with Trp and DTT, for at least 2 weeks
-
4C, 7-10 d, about 50% loss of activity
-
pH 7.0, anaerobically stored in 0.1 M potassium phosphate buffer containing L-Trp, quite stable
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
recombinant His-tagged enzyme by nickel affinity chromatography and gel filtration
-
Superdex 200 gel filtration
-
recombinant His6-tagged TDO from Escherichia coli strain BL21 (DE3) by nickel affinity chromatography and gel filtration to homogeneity
P20351
recombinant enzyme
-
recombinant enzyme, fusion protein to a hexahistidyl tag
-
the use of ALA, the biosynthetic precursor of protoporphyrin IX, coupled with metal-affinity chromatography and size exclusion chromatography produces 6His-IDP with a protein to heme ratio of 1:2.2
-
;
B3Y9H8, B3Y9H9
enzyme from intestine
-
expression of a fully functional enzyme in Escherichia coli
-
nickel-affinity and gel filtration chromatography
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Sf9 cells
Q17P71
expression of Ag-HisTDO in Escherichia coli
-
expressed in Escherichia coli
-
expression of recombinant His-tagged enzyme
-
GST-fusioned protein, expressed in Escherichia coli, expressed in HEK-293T cell
-
expression of His6-tagged TDO in Escherichia coli strain BL21 (DE3)
P20351
C-terminal hexahistidine tag, expressed in Escherichia coli
-
construction of recombinant replication-defective adenoviruses harboring the human indoleamine 2,3-dioxygenase gene and expression in dendritic cells
-
expressed in HeLa cells
-
expression in Escherichia coli
-
expression in Escherichia coli as a full-length, C-terminal hexahistidine fusion protein
-
expression in Escherichia coli EC538 as a fusion protein to a hexahistidyl tag
-
expression of His-tagged enzyme in Escherichia coli, optimised expression
-
hexa-histidine tag, expressed in Escherichia coli
-
quantitative real-time RT PCR enzyme expression analysis
-
hexahistidyl tagged, expressed in Escherichia coli, expressed in HEK-293T cell; hexahistidyl tagged, expressed in Escherichia coli, expressed in HEK-293T cell
B3Y9H8, B3Y9H9
cell-free transcription/translation using a wheat germ system, expression in COS-7 cell
-
expressed in HEK-293T cell
-
expression in COS-7 cells
P28776
quantitative real-time RT PCR enzyme expression analysis
-
hexahistidyl tagged, expressed in Escherichia coli, expressed in HEK-293T cell; hexahistidyl tagged, expressed in Escherichia coli, expressed in HEK-293T cell
B3Y9H6, B3Y9H7
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
-
expression in Escherichia coli
-
expressed in Escherichia coli
-
full-length enzyme is cloned into a pET-21d derivative, with a C-terminal hexahistidine tag, and overexpressed at 17C in Escherichia coli BL21(DE3) pMGK cells
-
hexahistidine tag, expressed in Escherichia coli BL21
-
GST-fusioned protein, expressed in Escherichia coli, expressed in HEK-293T cell
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
in mice heterozygous for the alpha-isoform of calcium/calmodulin-dependent protein kinase II, in which dentate gyrus granule cells fail to mature normally, TDO immunoreactivity is substantially downregulated in the dentate gyrus granule cells
-
TDO expression gradually increases with the development of granule cells. new neurons begin to express TDO between 2 and 4 weeks after the neurons are generated, when the axons and dendrites of the granule cells develop and synaptogenesis occurs
-
the expression of TDO mRNA is significantly increased in the cerebellum of Alzheimer's disease mouse brain
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Y42F
-
active site, tryptophan binding
H238A
-
mutant retains little or no heme, strong reduction of activity
H75A
-
mutant retains little or no heme, strong reduction of activity
H55A
-
kcat for L-Trp is 6.8fold lower than wild-type enzyme, KM-value is 1.7fold higher than wild-type value
H55A
-
active site, tryptophan binding
H55S
-
active site, tryptophan binding
T254A
-
ternary complex molecular simulations. The mutation causes the opening of the loop 250-260 to loop 117-130, leading to a more dynamic and open distal pocket, accounting for the much lower substrate affinity (i.e. higher Km). On the other hand, the simulation data of the ferryl/L-indole 2,3-epoxide intermediate indicate that the T254A mutation also results in the opening of the loop 250-260 to loop 117-130. It leads to local reorganization of the H-bonding interactions surrounding the NH3+ group of the substrate, resulting in an open conformation, in which the H-bond between the NH3+ and the epoxide is temporarily lost
H339A
-
used as negative control
H76A
-
active site, tryptophan binding
additional information
-
site-directed mutagenesis using the expression plasmid pQE9-IDO, to incorporate a stop codon at Lys389. This produces a C-terminally truncated protein, which lacks a mobile region. The Lys389 mutant retains enzymic activity
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
P20351
tryptophan 2,3-dioxygenase is considered as a drug target for cancer immunotherapy
medicine
-
yellowing of the aged lens may be preventable by drug-induced suppression of IDO activity
synthesis
-
production of 2,3-dihydro-1H-indole-2,3-diol