Information on EC 3.7.1.3 - kynureninase

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

EC NUMBER
COMMENTARY hide
3.7.1.3
-
RECOMMENDED NAME
GeneOntology No.
kynureninase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-kynurenine + H2O = anthranilate + L-alanine
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of C-C bond
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
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-kynurenine hydrolase
A pyridoxal-phosphate protein. Also acts on 3'-hydroxy-L-kynurenine and some other (3-arylcarbonyl)-alanines.
CAS REGISTRY NUMBER
COMMENTARY hide
9024-78-6
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain ATCC 19213
-
-
Manually annotated by BRENDA team
strain red blood
UniProt
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
constitutive enzyme
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
additional information
-
modeling of 3,5-dibromo-L-kynurenine in the active site of the human enzyme
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(2S)-2-amino-4-oxo-4-phenylbutanoic acid + H2O
benzoate + L-alanine
show the reaction diagram
-
the rate-determining step is Cbeta-Cgamma bond cleavage
-
-
?
(2S,3S)-erythro-beta-methyl-L-kynurenine
?
show the reaction diagram
-
-
-
?
(4R)-5-bromodihydro-L-kynurenine + H2O
? + L-alanine
show the reaction diagram
-
slow substrate, no activity with (4S)-5-bromodihydro-L-kynurenine
-
-
?
(4R)-dihydro-L-kynurenine + H2O
2-aminobenzaldehyde + L-alanine
show the reaction diagram
(alphaS,4R)-dihydrokynurenine + H2O
?
show the reaction diagram
-
the (alphaS,4R) diastereomer is a slow substrate for a retro-aldol reaction, and the (alphaS,4S) isomer is a potent competitive inhibitor, proposed mechanism for reaction of dihydrokynurenine
-
-
?
2-amino-4-(2-chlorophenyl)-4-oxobutanoic acid + H2O
?
show the reaction diagram
-
-
-
-
?
2-amino-4-(2-methoxyphenyl)-4-oxobutanoic acid + H2O
?
show the reaction diagram
-
-
-
-
?
2-amino-4-(4-methoxyphenyl)-4-oxobutanoic acid + H2O
?
show the reaction diagram
-
-
-
-
?
2-fluorobenzoyl-DL-alanine + H2O
2-fluorobenzoate + beta-alanine
show the reaction diagram
-
-
-
-
?
3,5-dibromo-L-kynurenine + H2O
3,5-dibromoanthranilate + DL-kynurenine
show the reaction diagram
3-bromo-L-kynurenine + H2O
3-bromoanthranilate + L-alanine
show the reaction diagram
3-chloro-DL-kynurenine + H2O
3-chloroanthranilate + DL-alanine
show the reaction diagram
3-fluoro-DL-kynurenine + H2O
3-fluoroanthranilate + DL-alanine
show the reaction diagram
3-hydroxy-DL-kynurenine + H2O
3-hydroxyanthranilate + DL-alanine
show the reaction diagram
-
-
-
?
3-hydroxy-L-kynurenine + H2O
3-hydroxyanthranilate + L-Ala
show the reaction diagram
3-hydroxy-L-kynurenine + H2O
3-hydroxyanthranilate + L-alanine
show the reaction diagram
3-methyl-DL-kynurenine + H2O
3-methylanthranilate + DL-alanine
show the reaction diagram
4-fluoro-L-kynurenine + H2O
4-fluoroanthranilate + L-alanine
show the reaction diagram
-
-
-
?
5-bromo-3-chloro-DL-kynurenine + H2O
5-bromo-3-chloroanthranilate + DL-alanine
show the reaction diagram
5-bromo-L-kynurenine + H2O
5-bromoanthranilate + L-alanine
show the reaction diagram
5-chloro-L-kynurenine + H2O
5-chloroanthranilate + L-alanine
show the reaction diagram
5-fluoro-L-kynurenine + H2O
5-fluoroanthranilate + L-alanine
show the reaction diagram
-
-
-
?
5-hydroxy-L-kynurenine + H2O
5-hydroxyanthranilate + L-alanine
show the reaction diagram
-
-
-
?
5-methyl-L-kynurenine + H2O
5-methylanthranilate + L-alanine
show the reaction diagram
-
-
-
?
beta-(4-chlorobenzoyl)-DL-alanine + H2O
4-chlorobenzoate + beta-alanine
show the reaction diagram
-
-
-
-
?
beta-(4-methylbenzoyl)-DL-alanine + H2O
4-methylbenzoate + beta-alanine
show the reaction diagram
-
-
-
-
?
beta-(4-trifluoromethylbenzoyl)-DL-alanine + H2O
4-trifluoromethylbenzoate + beta-alanine
show the reaction diagram
-
-
-
-
?
beta-benzoyl-DL-alanine + H2O
benzoate + DL-alanine
show the reaction diagram
-
-
-
?
beta-benzoyl-L-alanine + H2O
benzoate + L-alanine
show the reaction diagram
beta-chloro-L-alanine + H2O
?
show the reaction diagram
-
-
-
?
gamma-(o-aminophenyl)-L-homoserine + H2O
L-alanine + o-aminobenzaldehyde
show the reaction diagram
-
-
-
?
kynurenine + H2O
excitotoxin quinolinate
show the reaction diagram
-
-
-
?
kynurenine + H2O
quinolinate
show the reaction diagram
-
-
-
?
L-alanine + pyridoxal 5'-phosphate
pyruvate + pyridoxamine 5'-phosphate
show the reaction diagram
L-kynurenine + benzaldehyde
(2S,4R)-2-amino-4-hydroxy-4-phenylbutanoic acid + ?
show the reaction diagram
-
-
-
?
L-kynurenine + H2O
anthranilate + L-alanine
show the reaction diagram
L-ornithine + H2O
?
show the reaction diagram
-
-
-
?
more |
?
show the reaction diagram
for the bacterial enzyme, 3-methyl-, 3-halo- and 3,5-dihalokynurenines are much poorer substrates, while 3-fluoro, 5-bromo, and 5-chlorokynurenine have kcat and kcat/Km values comparable to that of its physiological substrate, L-kynurenine. 5-Bromo and 5-chloro-L-kynurenine are good substrates for the bacterial enzyme, indicating that the enzyme has space for substituents in the active site near C-5. The increased activity of the 5-halokynurenines may be due to van der Waals contacts or hydrophobic effects. The bacterial kynureninase cleaves L-kynurenine more rapidly than 3-hydroxy-L-kynurenine, substrate synthesis and specificity, overview
-
-
-
N-formyl-L-kynurenine + H2O
N-formylanthranilate + L-alanine
show the reaction diagram
O-benzoyl-L-serine + H2O
benzoate + pyruvate + ammonium
show the reaction diagram
-
O-benzoyl-L-serine is an alternate substrate for kynureninase, which undergoes a normal beta-elimination reaction, proposed mechanism for reaction of O-benzoyl-L-serine, overview
-
-
?
additional information
?
-
-
for the human enzyme, 3- and 5-substituted kynurenines have kcat and kcat/Km values higher than L-kynurenine, but less than that of the physiological substrate, 3-hydroxykynurenine. 3,5-Dibromo- and 5-bromo-3-chlorokynurenine have kcat and kcat/Km values close to that of 3-hydroxykynurenine with human kynureninase. The effects of the 3-halo substituents on the reactivity with human kynureninase may be due to electronic effects and/or halogen bonding. 5-Bromo and 5-chloro-L-kynurenine are good substrates the human enzyme, indicating that the enzyme has space for substituents in the active site near C-5. The increased activity of the 5-halokynurenines may be due to van der Waals contacts or hydrophobic effects. The mammalian kynureninase cleaves 3-hydroxy-L-kynurenine more rapidly than L-kynurenine, substrate synthesis and specificity, overview
-
-
-
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
3-hydroxy-L-kynurenine + H2O
3-hydroxyanthranilate + L-Ala
show the reaction diagram
3-hydroxy-L-kynurenine + H2O
3-hydroxyanthranilate + L-alanine
show the reaction diagram
5-hydroxy-L-kynurenine + H2O
5-hydroxyanthranilate + L-alanine
show the reaction diagram
-
-
-
?
5-methyl-L-kynurenine + H2O
5-methylanthranilate + L-alanine
show the reaction diagram
-
-
-
?
kynurenine + H2O
quinolinate
show the reaction diagram
-
-
-
?
L-alanine + pyridoxal 5'-phosphate
pyruvate + pyridoxamine 5'-phosphate
show the reaction diagram
L-kynurenine + H2O
anthranilate + L-alanine
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
pyridoxal 5'-phosphate
vitamin B6
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2S)-2-amino-4-oxo-4-phenylbutanoic acid
-
competitive inhibitor of the reaction of L-kynurenine with the enzyme
(4R)-5-bromodihydro-L-kynurenine
-
-
(4S)-5-bromodihydro-L-kynurenine
-
-
(4S)-dihydro-L-kynurenine
(alphaS,4S)-dihydrokynurenine
-
the (alphaS,4R) diastereomer is a slow substrate for a retro-aldol reaction, and the (alphaS,4S) isomer is a potent competitive inhibitor, proposed mechanism for reaction of dihydrokynurenine
-
(S)-(2-amino-4-bromophenyl)-L-cysteine S,S-dioxide
-
competitive inhibition
(S)-(2-amino-5-bromophenyl)-L-cysteine S,S-dioxide
-
competitive inhibition
(S)-(2-aminophenyl)-L-cysteine S,S-dioxide
-
-
2-amino-(4-oxo-4-naphthyl)-butyric acid
2-amino-3-fluoro-S-phenyl cysteine S,S-dioxide
-
-
2-amino-3-methoxy-S-phenyl cysteine S,S-dioxide
-
-
2-amino-4-[3'-hydroxyphenyl]-4-hydroxybutanoic acid
-
most potent inhibitor
2-amino-5-methyl-S-phenyl cysteine S,S-dioxide
-
-
2-amino-S-phenyl cysteine S,S-dioxide
-
-
3,5-dihydroxydeaminokynurenine
-
-
3,7-dihydroxy-deamino-DL-kynurenine
-
mixed inhibition
3-guanidino-L-alanine
-
0.001 mM in 0.2 mM Tris-HCl buffer
3-Hydroxy-DL-kynurenine
-
-
3-Hydroxyanthranilate
-
0.001 mM in 0.06 mM Tris-HCl buffer
3-hydroxydeaminokynurenine
3-hydroxyhippuric acid
3-methoxydeaminokynurenine
5-bromodihydrokynurenine
-
a potent transition-state analogue inhibitor
-
amino-(1-oxo-1,2,3,4-tetrahydro-2-naphthalenyl)-acetic acid
amino-(1-oxo-2,3-dihydro-1H-inden-2-yl)-acetic acid
amino-(4-oxo-3,4-dihydro-2H-chromen-3-yl)-acetic acid
anthranilic acid
benzaldehyde
benzoylalanine
-
-
beta-Alanine
-
competitive inhibition, 10 mM
beta-benzoyl-L-alanine
-
competitive inhibition, at 25C, pH 7.8
beta-chloro-L-alanine
cadaverine
D-alanine
-
competitive inhibition, 10 mM
D-cycloserine
D-kynurenine
D-penicillamine
D-serine
-
competitive inhibition, 10 mM
deaminokynurenine
-
competitive and non competitive inhibition
delta-N-acetyl-L-ornithine
dihydro-L-kynurenine
-
-
DL-5-chloro-kynurenine
-
substantially inhibits
DL-allothreonine
-
competitive inhibition, 10 mM
DL-alpha-aminobutyric acid
-
competitive inhibition, 10 mM
DL-dihydroxyphenylalanine
DL-homoserine
-
competitive inhibition, 10 mM
DL-methionine
-
competitive inhibition, 40 mM
DL-Ornithine
-
competitive inhibition, 10 mM
iodoacetate
-
0.5 mM
Kynurenate
L-5-chloro-kynurenine
-
substantially inhibits
L-alanine
L-arginine
-
competitive inhibition, 10 mM
L-asparagine
-
competitive inhibition, 10 mM
L-aspartic acid
-
competitive inhibition, 10 mM
L-cysteine
-
competitive inhibition, 10 mM
L-Glutamic acid
-
competitive inhibition, 10 mM
L-glutamine
-
competitive inhibition, 10 mM
L-histidine
-
competitive inhibition, 10 mM
L-kynurenine
L-lysine
L-ornithine
L-Penicillamine
-
-
L-serine
-
competitive inhibition, 10 mM
L-threonine
-
competitive inhibition, 10 mM
L-tryptophan
-
competitive inhibition, 10 mM
lanthellamide
-
about 60% residual activity at 1 mM, about 80% residual activity at 0.5 mM, slight inhibition at 0.125 mM
m-nitrobenzoylalanine
-
-
N'-formyl-L-kynurenine
-
-
N-ethylmaleimide
-
1 mM
NaHSO3
-
1 mM
nicotinylalanine
o-aminoacetophenone
o-aminobenzaldehyde
o-bromobenzoylalanine
-
-
o-ethoxybenzoylalanine
-
-
o-fluorobenzoylalanine
-
-
o-methoxybenzoylalanine
-
-
o-methylbenzoylalanine
-
-
o-nitrobenzaldehyde
o-trifluoromethylbenzoylalanine
-
-
p-chloromercuribenzoate
p-hydroxyphenylpyruvate
-
5 mM
phenylhydrazine-HCl
phenylpyruvate
-
1 mM
putrescine
pyridoxal 5'-phosphate
-
-
quinaldinate
S-(2-aminophenyl)-L-cysteine dioxide
-
-
-
S-(2-aminophenyl)-L-cysteine S,S-dioxide
S-(beta-aminoethyl)-L-cysteine
-
0.001 mM in 0.06 mM Tris-HCl buffer
Semicarbazide
Sodium borohydride
tryptamine
-
competitive inhibition, 10 mM
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
pyridoxal 5'-phosphate
pyridoxamine phosphate
-
in the presence of pyruvate
additional information
-
kynurenine induces both tryptophan oxygenase and kynureninase of the catabolic pathway of L-tryptophan degradation
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2
3-bromo-L-kynurenine
-
-
0.0283
3-Hydroxy-DL-kynurenine
-
-
0.003 - 3
3-hydroxy-L-kynurenine
0.0039 - 0.0067
3-hydroxykynurenine
0.067
4-fluoro-L-kynurenine
-
-
0.011
5-bromo-L-kynurenine
-
-
0.048
5-fluoro-L-kynurenine
-
-
0.008
beta-benzoyl-L-alanine
-
at 25C, pH 7.8
0.16
beta-benzoyl-L-kynurenine
-
-
0.067
gamma-(o-aminophenyl)-L-homoserine
-
-
0.006 - 0.08
kynurenine
0.013 - 0.54
L-3-hydroxykynurenine
11
L-alanine
-
-
0.0067 - 1
L-kynurenine
40
L-ornithine
-
-
2.2
N'-formyl-L-kynurenine
0.0018
pyridoxal 5'-phosphate
-
-
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.7
(2S)-2-amino-4-oxo-4-phenylbutanoic acid
Pseudomonas fluorescens
-
at pH 7.8
0.08
2-amino-4-(2-chlorophenyl)-4-oxobutanoic acid
Pseudomonas fluorescens
-
at 37C in 0.04 M potassium phosphate, pH 7.8
-
0.05
2-amino-4-(2-methoxyphenyl)-4-oxobutanoic acid
Pseudomonas fluorescens
-
at 37C in 0.04 M potassium phosphate, pH 7.8
-
0.38
2-amino-4-(4-methoxyphenyl)-4-oxobutanoic acid
Pseudomonas fluorescens
-
at 37C in 0.04 M potassium phosphate, pH 7.8
-
0.06
2-fluorobenzoyl-DL-alanine
Pseudomonas fluorescens
-
at 37C in 0.04 M potassium phosphate, pH 7.8
-
0.23 - 1.2
3,5-dibromo-L-kynurenine
1.9 - 11
3-bromo-L-kynurenine
0.67 - 0.71
3-chloro-DL-kynurenine
0.23 - 6.9
3-fluoro-DL-kynurenine
3.5
3-Hydroxy-DL-kynurenine
Homo sapiens
-
-
0.0039 - 3.5
3-hydroxy-L-kynurenine
0.33 - 1.5
3-methyl-DL-kynurenine
1.3 - 6.3
5-bromo-3-chloro-DL-kynurenine
0.63 - 11.9
5-bromo-L-kynurenine
0.47 - 8.7
5-chloro-L-kynurenine
1.83
beta-(4-chlorobenzoyl)-DL-alanine
Pseudomonas fluorescens
-
at 37C in 0.04 M potassium phosphate, pH 7.8
0.91
beta-(4-methylbenzoyl)-DL-alanine
Pseudomonas fluorescens
-
at 37C in 0.04 M potassium phosphate, pH 7.8
0.001
beta-(4-trifluoromethylbenzoyl)-DL-alanine
Pseudomonas fluorescens
-
at 37C in 0.04 M potassium phosphate, pH 7.8
0.7
beta-benzoyl-L-alanine
Pseudomonas fluorescens
-
-
0.0058 - 16
L-kynurenine
0.1 - 2.5
O-benzoyl-L-serine
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
12
2-amino-4-(2-chlorophenyl)-4-oxobutanoic acid
Pseudomonas fluorescens
-
at 37C in 0.04 M potassium phosphate, pH 7.8
88220
1.4
2-amino-4-(2-methoxyphenyl)-4-oxobutanoic acid
Pseudomonas fluorescens
-
at 37C in 0.04 M potassium phosphate, pH 7.8
88221
1.6
2-amino-4-(4-methoxyphenyl)-4-oxobutanoic acid
Pseudomonas fluorescens
-
at 37C in 0.04 M potassium phosphate, pH 7.8
88219
1.7
2-fluorobenzoyl-DL-alanine
Pseudomonas fluorescens
-
at 37C in 0.04 M potassium phosphate, pH 7.8
88218
7.9 - 21
3,5-dibromo-L-kynurenine
4.4 - 5.5
3-bromo-L-kynurenine
8.2 - 11
3-chloro-DL-kynurenine
2.7 - 90
3-fluoro-DL-kynurenine
2.5 - 123
3-hydroxy-L-kynurenine
1.8 - 22
3-methyl-DL-kynurenine
6.5 - 22
5-bromo-3-chloro-DL-kynurenine
1.5 - 3300
5-bromo-L-kynurenine
1.1 - 1800
5-chloro-L-kynurenine
18
beta-(4-chlorobenzoyl)-DL-alanine
Pseudomonas fluorescens
-
at 37C in 0.04 M potassium phosphate, pH 7.8
88216
28
beta-(4-methylbenzoyl)-DL-alanine
Pseudomonas fluorescens
-
at 37C in 0.04 M potassium phosphate, pH 7.8
88215
0.019
beta-(4-trifluoromethylbenzoyl)-DL-alanine
Pseudomonas fluorescens
-
at 37C in 0.04 M potassium phosphate, pH 7.8
88217
0.465 - 600
L-kynurenine
0.0041 - 11
O-benzoyl-L-serine
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.01
(2S)-2-amino-4-oxo-4-phenylbutanoic acid
-
reaction of L-kynurenine with the enzyme
0.000055
(4R)-5-bromodihydro-L-kynurenine
-
-
0.00017
(4S)-5-bromodihydro-L-kynurenine
-
-
0.0003
(S)-(2-amino-4-bromophenyl)-L-cysteine S,S-dioxide
-
-
0.0004
(S)-(2-amino-5-bromophenyl)-L-cysteine S,S-dioxide
-
-
0.000027
(S)-(2-aminophenyl)-L-cysteine S,S-dioxide
-
-
0.005 - 0.022
2-amino-(4-oxo-4-naphthyl)-butyric acid
0.175
2-amino-4-(3-methoxyphenyl)-4-oxobutanoic acid
-
-
0.00025
3,5-dihydroxydeaminokynurenine
-
-
0.000005 - 0.00004
3-hydroxydeaminokynurenine
0.01 - 0.015
3-methoxydeaminokynurenine
0.17 - 0.227
amino-(1-oxo-1,2,3,4-tetrahydro-2-naphthalenyl)-acetic acid
0.0349 - 0.045
amino-(1-oxo-2,3-dihydro-1H-inden-2-yl)-acetic acid
0.077 - 0.162
amino-(4-oxo-3,4-dihydro-2H-chromen-3-yl)-acetic acid
0.01
beta-benzoyl-L-alanine
-
at 25C, pH 7.8
0.012
D-kynurenine
0.02 - 0.055
L-kynurenine
0.00003 - 0.00092
S-(2-aminophenyl)-L-cysteine dioxide
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00001
-
kidney, approximately
0.000018
-
liver
0.000019
-
liver of diet-induced hyperlipidemic animals
0.00002
-
kidney; liver of normolipidemic animals
0.000021
-
kidney of normolipidemic animals
0.000022
-
kidney of diet-induced hyperlipidemic animals
0.00003
-
liver, kidney, approximate values
0.00004
-
liver, approximately
0.00006
-
liver, kidney, approximate values
0.00009
-
liver, kidney, approximate values
0.0002
-
liver
0.0007
-
liver
0.008 - 0.015
-
pH 7.5, 37C
0.026
-
liver
0.164
-
pH 7.9, 37C
0.661
-
-
1.2 - 2.2
-
pH 7.5, 37C
1.75
-
3-hydroxy-DL-kynurenine
4.4
-
cells grown on L-asparagine
8.8
-
cells grown on L-arginine
10.3
-
cells grown on L-alanine
31.25
-
cells grown on L-tryptophan
68.3
-
-
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.8 - 8.5
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 9.5
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
cells grown in a medium containing L-tryptophan as the sole carbon, nitrogen, and energy source
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45820
-
MALDI-TOF
48600
calculated from amino acid sequence
49000
approximately 49000 Da, SDS-PAGE
91000
-
gel filtration
92000
-
gel filtration
100000
105000
110000
130000
-
-
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
-
native enzyme, 2 * 52500, disc gel electrophoresis
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
no modification
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystals of recombinant kynureninase that diffracted to 2.0 A are obtained, and the atomic structure of the PLP-bound holoenzyme is determined by molecular replacement using the Pseudomonas fluorescens structure as the phasing model
-
the wild type enzyme is cocrystallized with 3-hydroxyhippuric acid, using the modified microbatch under oil technique at 25?C, with 0.05 M MgCl2, 0.1 M Tris (pH 8.0), and 25% (w/v) PEG 3000
-
by hanging-drop vapor diffusion method at room temperature, to 1.85 A resolution, Lys-227 is the pyridoxal-5'-phosphate binding residue near the pyridoxal-5'-phosphate nitrogen, but Asp-132 is also strictly conserved and at a similar distance from the pyridinium nitrogen, Tyr-226 donates a hydrogen bond to the phosphate of pyridoxal-5'-phosphate, Trp-256 donates a hydrogen bond to the phosphate through the indole N1-hydrogen; performed using the hanging-drop vapor diffusion technique
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.2
-
-
289259
5.8 - 8
-
-
289263
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-78C, 0.1 mM potassium phosphate buffer, 0.2 mM pyridoxal 5'-phosphate, pH 8.0, 1 year, stable
-78C, 5 mM potassium phosphate buffer, 0.2 mM pyridoxal 5'-phosphate, pH 8.0, 1 month, loses 4% of activity
-80C, pyridoxal 5'-phosphate, more than 12 months, no loss of activity
-
-80C, without pyridoxal 5'-phosphate, more than 12 months, no loss of activity
-
4C, phosphate buffer, pH 7.2, 0.02 mM pyridoxal-5'-phosphate, 1 week
-
4C, 5 mM potassium phosphate buffer, 0.2 mM pyridoxal 5'-phosphate, pH 8.0, 1 week, loses 40% of activity
4C, pyridoxal 5'-phosphate, up to 2 weeks, stable
-
70% saturated solution of ammonium sulfate containing 1 mM EDTA, 1 mM dithiothreitol, and 0.05 mM pyridoxal 5'-phosphate, 2 months
-
78C, phosphate buffer, 1 year
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
; by chromatography on phenyl-Sepharose
-
; recombinant enzyme, by centrifugation, protamine sulfate precipitation, HiTrap Q column, omega-aminohexylagarose column, second HiTrap Q column and phenyl-Sepharose column
by protamine sulfate precipitation, ammonium sulfate precipitation, DEAE-Sepharose 6B column, Sephadex G-100 column, Mono-Q HR 5/5 column, 50-80fold
-
by strong cationic column, strong anion exchange column and hydroxyapatite column
-
constitutive and inducible enzyme
-
His GraviTrap nickel affinity column chromatography
recombinant enzyme from Escherichia coli strain BL21(DE3)
-
recombinant enzyme from Escherichia coli strain DH5alpha
recombinant enzyme, ammonium sulfate precipitation, DEAE-Sepharose CL-6B affinity column, hydroxyapatite column, strong anion-exchange column at pH 8.6, strong cation-exchange column at pH 6.0 strong anion-exchange column at pH 6.0, 60fold
-
using a Ni-CAM resin column
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
expressed in Escherichia coli DH-5alpha cells
-
expression in Escherichia coli; into vector pTZKYN and transformed in Escherichia coli XL-1 Blue cells
-
expression in Escherichia coli; subcloned into pSapKO-WT and transformed into Escherichia coli B834(DE3)
expression in Sf9 insect cells
-
expression in Spodoptera frugiperda cells
-
expression of the recombinant enzyme in Escherichia coli strain BL21(DE3)
-
expression of the recombinant enzyme in Escherichia coli strain DH5alpha
into a pET100 plasmid for expression in Escherichia coli BL21DE3 cells
-
overexpression is achieved with the Bac-to-Bac baculovirus expression system
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
T102I
the mutation leads to a marked decrease in kynureninase activity and causes the red body coloration in the Bombyx mori red blood strain
H102W/N333T
-
the mutant shows complete reversal of substrate specificity between 3-hydroxy-L-kynurenine and L-kynurenine
H102W/S332G/N333T
-
the mutant shows complete reversal of substrate specificity between 3-hydroxy-L-kynurenine and L-kynurenine
N333T
-
the mutant reveals a 9fold decrease in kcat for L-kynurenine, but no change in Km, the mutant has weaker 3-hydroxy-L-kyrenine binding (6fold higher Km) and kcat at least 1100times slower than wild type Kynase
S332G/N333T the
-
mutant shows a very slight preference for L-kynurenine over 3-hydroxy-L-kynurenine
T198A
-
screening of cDNA from KYNU revealed homozygosity for a c.593A>G substitution in exon 7 in the proband, leading to a threonine-to-alanine shift, T198A, in kynureninase
D132A
has lower activity and binds pyridoxal 5'-phosphate weakly; has lower activity and weaklier pyridoxal-5'-phosphate binding than that of wild-type enzyme
D132E
has good activity and pyridoxal 5'-phosphate binding stronger than that of the wild-type enzyme; has good activity and stronger pyridoxal-5'-phosphate binding than that of wild-type enzyme
D201A
has very low activity and binds pyridoxal-5'-phosphate weakly, and expresses poorly, giving large amounts of insoluble inclusion bodies and very low levels of soluble protein; has very low activity, less than 0.01% of that of the wild-type enzyme, binds pyridoxal 5'-phosphate weakly
D201E
has good activity and pyridoxal 5'-phosphate binding stronger than that of the wild-type enzyme; has good activity and stronger pyridoxal-5'-phosphate binding than that of wild-type enzyme
Y226F
-
site-directed mutagenesis, the mutant has approximately 3000fold lower activity than wild-type, and does not show the pKa values of 6.8 on kcat and 6.5 and 8.8 on kcat/Km seen for the wild-type enzyme
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
medicine
synthesis
additional information