Information on EC 1.13.11.11 - tryptophan 2,3-dioxygenase

for references in articles please use BRENDA:EC1.13.11.11
Word Map on EC 1.13.11.11
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Select one or more organisms in this record:


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

EC NUMBER
COMMENTARY hide
1.13.11.11
-
RECOMMENDED NAME
GeneOntology No.
tryptophan 2,3-dioxygenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-tryptophan + O2 = N-formyl-L-kynurenine
show the reaction diagram
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
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)
-
-
tryptophan metabolism
-
-
Tryptophan metabolism
-
-
Metabolic pathways
-
-
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].
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
no activity in Brugia malayi
-
-
-
Manually annotated by BRENDA team
no activity in Saccharomyces cerevisiae
-
-
-
Manually annotated by BRENDA team
no activity in Schistosoma mansoni
-
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
5-fluoro-L-tryptophan + O2
5-fluoro-N-formyl-L-kynurenine
show the reaction diagram
D-tryptophan + O2
N-formyl-D-kynurenine
show the reaction diagram
indole-3-pyruvic acid + O2
?
show the reaction diagram
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
D-tryptophan + O2
N-formyl-D-kynurenine
show the reaction diagram
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-(2-methylbenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
-
-
1-(3-bromobenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
-
-
1-(3-chlorobenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
-
-
1-(3-[(4-acetyl-1-piperazinyl)carbonyl]benzyl)-1H-naphtho-[2,3-d][1,2,3]triazole-4,9-dione
-
-
1-(3-[(4-methyl-1-piperazinyl)carbonyl]benzyl)-1H-naphtho-[2,3-d][1,2,3]triazole-4,9-dione
-
-
1-(4-bromobenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
-
-
1-(4-fluorobenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
-
-
1-(4-methylbenzyl)-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
-
-
1-(4-[(4-acetylpiperazin-1-yl)carbonyl]benzyl)-1H-naphtho-[2,3-d][1,2,3]triazole-4,9-dione
-
-
1-(4-[(4-methoxypiperidin-1-yl)carbonyl]benzyl)-1Hnaphtho[2,3-d][1,2,3]triazole-4,9-dione
-
-
1-[(3-methylphenyl)methyl]-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
-
-
1-[(4-chlorophenyl)methyl]-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione
-
-
1-[3-(4-morpholinylcarbonyl)benzyl]-1H-naphtho[2,3-d]-[1,2,3]triazole-4,9-dione
-
-
1-[4-(morpholin-4-ylcarbonyl)benzyl]-1H-naphtho[2,3-d]-[1,2,3]triazole-4,9-dione
-
-
1-[4-[(4-methylpiperazin-1-yl)carbonyl]benzyl]-1H-naphtho-[2,3-d][1,2,3]triazole-4,9-dione
-
-
2-(4-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]-triazol-1-yl)methyl]phenyl)-N,N-diethylacetamide
-
-
3-hydroxykynurenine
-
3-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)methyl]-N,N-diethylbenzamide
-
-
3-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)methyl]benzoic acid
-
-
4-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)methyl]-N,N-diethylbenzamide
-
-
4-[(4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d][1,2,3]triazol-1-yl)methyl]benzoic acid
-
-
isatin
-
mechanism of inhibition
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
H2O2
activation of the enzyme is stimulated by superoxide and H2O2
superoxide
activation of the enzyme is stimulated by superoxide and H2O2
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.02 - 1.531
L-tryptophan
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.01 - 1071
L-tryptophan
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
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
0.001745
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
0.000048
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
0.00009
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
0.000181
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
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
low level expression
Manually annotated by BRENDA team
low level expression
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Cupriavidus metallidurans (strain ATCC 43123 / DSM 2839 / NBRC 102507 / CH34)
Xanthomonas campestris pv. campestris (strain ATCC 33913 / DSM 3586 / NCPPB 528 / LMG 568 / P 25)
Xanthomonas campestris pv. campestris (strain ATCC 33913 / DSM 3586 / NCPPB 528 / LMG 568 / P 25)
Xanthomonas campestris pv. campestris (strain ATCC 33913 / DSM 3586 / NCPPB 528 / LMG 568 / P 25)
Xanthomonas campestris pv. campestris (strain ATCC 33913 / DSM 3586 / NCPPB 528 / LMG 568 / P 25)
Xanthomonas campestris pv. campestris (strain ATCC 33913 / DSM 3586 / NCPPB 528 / LMG 568 / P 25)
Xanthomonas campestris pv. campestris (strain ATCC 33913 / DSM 3586 / NCPPB 528 / LMG 568 / P 25)
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
-
apo hTDO
tetramer
additional information
-
hTDO must form an oligomer to exhibit activity. Active site structure, overview
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 Tris–HCl, 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
-
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
-
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)
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
F140A
-
site-directed mutagenesis, the mutant shows 0.25% of wild-type activity
F72A
-
site-directed mutagenesis, inactive mutant
H328A
-
site-directed mutagenesis, inactive mutant
H76A,
-
site-directed mutagenesis, inactive mutant
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
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
-
the enzyme is a target for drug development
medicine
-
the enzyme is a therapeutic target in cancer treatment
Show AA Sequence (4525 entries)
Please use the Sequence Search for a specific query.