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 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
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
redox reaction
reduction
-
-
-
-
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)
-
-
Metabolic pathways
-
-
tryptophan metabolism
-
-
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].
CAS REGISTRY NUMBER
COMMENTARY hide
9014-51-1
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
Uniprot
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain ATCC 19213
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Frog
-
-
-
Manually annotated by BRENDA team
-
-
-
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
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
the kynurenine pathway is over-activated in Alzheimer's disease mice
metabolism
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
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
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
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
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
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-Trp + O2
D-formylkynurenine
show the reaction diagram
-
-
-
?
D-Trp + O2
N-formyl-D-kynurenine
show the reaction diagram
D-tryptophan + O2
N-formyl-D-kynurenine
show the reaction diagram
DL-5-fluoro-methyltryptophan + O2
?
show the reaction diagram
DL-5-methyltryptophan + O2
?
show the reaction diagram
DL-6-fluorotryptophan + O2
?
show the reaction diagram
DL-6-methyltryptophan
?
show the reaction diagram
DL-alpha-methyltryptophan + O2
alpha-methyl-N-formyl-DL-kynurenine
show the reaction diagram
-
9.0% of the activity with L-Trp
-
-
?
indole + 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
N-formyl-L-kynurenine
show the reaction diagram
-
-
-
?
L-tryptophan + O2
N-formyl-L-kynurenine
show the reaction diagram
L-tryptophan + O2
N-formylkynurenine
show the reaction diagram
serotonin + O2
?
show the reaction diagram
tryptamine + O2
?
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
-
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
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
Cd2+
-
0.007-0.1 mM, maximal stimulation at 0.007 mM
copper
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(E)-6-fluoro-3-[2-(3-pyridyl)vinyl]-1H-indole
-
-
1-L-methyltryptophan
1-methyl-D-tryptophan
-
1-methyl-DL-Trp
-
-
1-Methyltryptophan
2-methylindole
-
-
3-hydroxyanthranilic acid
-
-
3-hydroxykynurenine
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
actinomycin D
-
-
acyclovir
-
-
Bathocuproinesulfonate
-
competitive with respect to L-Trp and noncompetitive with respect to O2
Cd2+
-
0.5-1.0 mM, non-competitive
Cinnabarinic acid
-
-
Cu2+
-
0.005 mM, 50% inhibition
diethyldithiocarbamate
DL-4-fluorotryptophan
DL-4-methyltryptophan
DL-5-fluorotryptophan
DL-5-hydroxytryptophan
-
1 mM, 55% inhibition
DL-5-Methyltryptophan
DL-alpha-methyltryptophan
-
-
ferricyanide
-
-
hydroxylamine
indole
Indolepropionic acid
K3Fe(CN)6
-
1 mM, complete inhibition
Kynurenic acid
-
0.1 mM, 57.2% inhibition. 1 mM, 99.4% inhibition
L-5-hydroxytryptophan
L-kynurenine
-
0.1 mM, 17.7% inhibition. 1 mM, 93.6% inhibition
L-Trp
-
above 8 mM
L-tryptophan
-
substrate inhibition (above 0.05 mM)
N1-acetyl-N2-formyl-5-methoxykynurenine
-
-
NADH
-
0.1 mM, 51.3% inhibition
norharman
-
2 mM, 98% inhibition, uncompetitive
O2
-
inhibition of mutant forms H55A and H55S at high concentrations
potassium cyanide
-
-
Sodium azide
-
-
Superoxide dismutase
-
-
-
tryptamine
xanthurenic acid
-
0.1 mM, 50.6% inhibition. 1 mM, 96.2% inhibition
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
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
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
methylene blue
methylhydroperoxide
-
can reduce the inactive ferric form of the enzyme to the active ferrous form
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
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.1 - 100
5-fluoro-DL-tryptophan
0.36
5-fluoro-tryptophan
-
-
0.6
5-hydroxy-D-tryptophan
-
24C
0.02 - 0.44
5-hydroxy-L-tryptophan
0.357 - 1.302
5-methyl-DL-tryptophan
0.186 - 186
6-fluoro-DL-tryptophan
0.386 - 1.98
6-methyl-DL-tryptophan
0.3 - 5.2
D-Trp
0.18 - 16
D-tryptophan
30.27
indole
-
-
0.02 - 133
L-Trp
0.0063 - 62.4
L-tryptophan
0.037 - 119
O2
0.1 - 2.56
serotonin
0.075
tryptamine
-
24C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.68 - 2.4
5-fluoro-DL-tryptophan
0.18
5-fluoro-tryptophan
Homo sapiens
-
-
0.00967
5-hydroxy-D-tryptophan
Oryctolagus cuniculus
-
24C
0.0433 - 0.065
5-hydroxy-L-tryptophan
0.4 - 3.59
5-methyl-DL-tryptophan
3.78 - 37.3
6-fluoro-DL-tryptophan
1.65 - 41
6-methyl-DL-tryptophan
1.18 - 2.07
D-Trp
0.0068 - 0.2
D-tryptophan
0.248
indole
Micromonospora sp.
-
-
1.55 - 19.5
L-Trp
0.04 - 35.4
L-tryptophan
35.4
O2
Xanthomonas campestris
-
25C, pH 7.5, wild-type enzyme
0.00283 - 0.028
serotonin
0.00483
tryptamine
Oryctolagus cuniculus
-
24C
additional information
additional information
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
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 - 1
DL-4-fluorotryptophan
0.28 - 0.67
DL-4-methyltryptophan
0.12 - 0.39
DL-5-fluorotryptophan
0.19 - 0.55
DL-5-Methyltryptophan
0.14 - 2.7
indole
0.08 - 0.21
Indolepropionic acid
0.001 - 0.01
L-5-hydroxytryptophan
0.17
L-tryptophan
-
-
0.176
norharman
-
-
0.48 - 1.38
O2
0.1 - 1.8
tryptamine
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
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
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
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
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.4
-
calculated from sequence
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
detectable immunohistochemically from day 6
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
-
extravillous
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
-
BAOEC cell
Manually annotated by BRENDA team
-
of uterine endometrium and cervix
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
-
Langerhans cells possess an immunoregulatory function in promoting T cell tolerance by production of IDO
Manually annotated by BRENDA team
-
IFNgamma-primed
Manually annotated by BRENDA team
-
premetamorphic stage
Manually annotated by BRENDA team
-
epithelium
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)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
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
122000
-
gel filtration, sucrose density gradient centrifugation, equilibrium sedimentation
123000
-
low speed equilibrium sedimentation
160000 - 180000
-
gel filtration, sucrose density gradient centrifugation
167000
190000
additional information
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homotetramer
monomer
tetramer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
Crystallization/COMMENTARY
ORGANISM
UNIPROT
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
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
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4
-
4C, 6 h, 52% loss of activity
395462
5
-
4C, 6 h, 7% loss of activity
395462
6
-
4C, no loss of activity after 6 h
395462
6.5
-
most stable at
395490
7
-
4C, 6 h, 15% loss of activity
395462
8
-
4C, 6 h, 55% loss of activity
395462
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
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
LITERATURE
enzyme is most stable in presence of L-Trp or alpha-methyl-DL-tryptophan, and in absence of oxygen
-
freezing and thawing causes 66% loss of activity
-
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
-
unstable in purified state, if the substrate is omitted during the last step, the activity is lost entirely
-
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
-
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
most stable in absence of oxygen
-
395489
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70C, stable for at least 2 months
-
-9C, pH 7, stable in 0.1 M phosphate buffer with Trp and DTT, for at least 2 weeks
-
0C, under anaerobic conditions in presence of tryptophan, stable for several days
-
4C, 7-10 d, about 50% loss of activity
-
5C, 48 h, 23% loss of activity
-
pH 7.0, anaerobically stored in 0.1 M potassium phosphate buffer containing L-Trp, quite stable
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
enzyme from intestine
-
expression of a fully functional enzyme in Escherichia coli
-
nickel-affinity and gel filtration chromatography
-
recombinant enzyme
-
recombinant enzyme, fusion protein to a hexahistidyl tag
-
recombinant His-tagged enzyme by nickel affinity chromatography and gel filtration
-
recombinant His6-tagged TDO from Escherichia coli strain BL21 (DE3) by nickel affinity chromatography and gel filtration to homogeneity
Superdex 200 gel filtration
-
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
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
C-terminal hexahistidine tag, expressed in Escherichia coli
-
cell-free transcription/translation using a wheat germ system, expression in COS-7 cell
-
construction of a cDNA clone and its use in isolating genomic clones containing the structural gene
-
construction of recombinant replication-defective adenoviruses harboring the human indoleamine 2,3-dioxygenase gene and expression in dendritic cells
-
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
-
expressed in Escherichia coli
expressed in HEK-293T cell
-
expressed in HeLa cells
-
expression in COS-7 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 in Sf9 cells
expression of Ag-HisTDO in Escherichia coli
-
expression of His-tagged enzyme in Escherichia coli, optimised expression
-
expression of His6-tagged TDO in Escherichia coli strain BL21 (DE3)
expression of recombinant His-tagged enzyme
-
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
-
GST-fusioned protein, expressed in Escherichia coli, expressed in HEK-293T cell
hexa-histidine tag, expressed in Escherichia coli
-
hexahistidine tag, expressed in Escherichia coli BL21
-
hexahistidyl tagged, expressed in Escherichia coli, expressed in HEK-293T cell; hexahistidyl tagged, expressed in Escherichia coli, expressed in HEK-293T cell
quantitative real-time RT PCR enzyme expression analysis
EXPRESSION
ORGANISM
UNIPROT
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
COMMENTARY hide
LITERATURE
H76A
-
active site, tryptophan binding
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
H55S
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active site, tryptophan binding
T254A
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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
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used as negative control
additional information
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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
COMMENTARY hide
LITERATURE
medicine
synthesis
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production of 2,3-dihydro-1H-indole-2,3-diol
Show AA Sequence (2193 entries)
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