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Literature summary for 3.7.1.3 extracted from

  • Maitrani, C.; Phillips, R.S.
    Substituents effects on activity of kynureninase from Homo sapiens and Pseudomonas fluorescens (2013), Bioorg. Med. Chem., 21, 4670-4677.
    View publication on PubMed
Search for more literature for 3.7.1.3

Application

Application Comment Organism
drug development the enzym eis a target for the design of potent and/or selective inhibitors of bacterial kynureninase Pseudomonas fluorescens
drug development the enzyme is a target for the design of potent and/or selective inhibitors of human kynureninase Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
expression of the recombinant enzyme in Escherichia coli strain BL21(DE3) Homo sapiens
expression of the recombinant enzyme in Escherichia coli strain DH5alpha Pseudomonas fluorescens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information kinetic analysis of kynurenine analogues, overview Homo sapiens
additional information
-
 additional information kinetic analysis of kynurenine analogues, overview Pseudomonas fluorescens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3-hydroxy-L-kynurenine + H2O Homo sapiens
-
 3-hydroxyanthranilate + L-alanine
-
 ?
L-kynurenine + H2O Pseudomonas fluorescens
-
 anthranilate + L-alanine
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q16719
-
-
Pseudomonas fluorescens P83788 gene kynU
-

Purification (Commentary)

Purification (Comment) Organism
recombinant enzyme from Escherichia coli strain BL21(DE3) Homo sapiens
recombinant enzyme from Escherichia coli strain DH5alpha Pseudomonas fluorescens

Reaction

Reaction Comment Organism Reaction ID
L-kynurenine + H2O = anthranilate + L-alanine catalytic reaction mechanism via several intermediates, e.g. external aldimine, quinonoid, ketimine, Gem-diolate, and enamine Homo sapiens
a
L-kynurenine + H2O = anthranilate + L-alanine catalytic reaction mechanism via several intermediates, e.g. external aldimine, quinonoid, ketimine, Gem-diolate, and enamine Pseudomonas fluorescens
a

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3,5-dibromo-L-kynurenine + H2O
-
 Homo sapiens 3,5-dibromoanthranilate + DL-kynurenine
-
 ?
3,5-dibromo-L-kynurenine + H2O
-
 Pseudomonas fluorescens 3,5-dibromoanthranilate + DL-kynurenine
-
 ?
3-bromo-L-kynurenine + H2O
-
 Homo sapiens 3-bromoanthranilate + L-alanine
-
 ?
3-bromo-L-kynurenine + H2O
-
 Pseudomonas fluorescens 3-bromoanthranilate + L-alanine
-
 ?
3-chloro-DL-kynurenine + H2O
-
 Homo sapiens 3-chloroanthranilate + DL-alanine
-
 ?
3-chloro-DL-kynurenine + H2O
-
 Pseudomonas fluorescens 3-chloroanthranilate + DL-alanine
-
 ?
3-fluoro-DL-kynurenine + H2O
-
 Homo sapiens 3-fluoroanthranilate + DL-alanine
-
 ?
3-fluoro-DL-kynurenine + H2O
-
 Pseudomonas fluorescens 3-fluoroanthranilate + DL-alanine
-
 ?
3-hydroxy-L-kynurenine + H2O
-
 Homo sapiens 3-hydroxyanthranilate + L-alanine
-
 ?
3-hydroxy-L-kynurenine + H2O
-
 Pseudomonas fluorescens 3-hydroxyanthranilate + L-alanine
-
 ?
3-methyl-DL-kynurenine + H2O
-
 Homo sapiens 3-methylanthranilate + DL-alanine
-
 ?
3-methyl-DL-kynurenine + H2O
-
 Pseudomonas fluorescens 3-methylanthranilate + DL-alanine
-
 ?
5-bromo-3-chloro-DL-kynurenine + H2O
-
 Homo sapiens 5-bromo-3-chloroanthranilate + DL-alanine
-
 ?
5-bromo-3-chloro-DL-kynurenine + H2O
-
 Pseudomonas fluorescens 5-bromo-3-chloroanthranilate + DL-alanine
-
 ?
5-bromo-L-kynurenine + H2O
-
 Homo sapiens 5-bromoanthranilate + L-alanine
-
 ?
5-bromo-L-kynurenine + H2O
-
 Pseudomonas fluorescens 5-bromoanthranilate + L-alanine
-
 ?
5-chloro-L-kynurenine + H2O
-
 Homo sapiens 5-chloroanthranilate + L-alanine
-
 ?
5-chloro-L-kynurenine + H2O
-
 Pseudomonas fluorescens 5-chloroanthranilate + L-alanine
-
 ?
L-kynurenine + H2O
-
 Homo sapiens anthranilate + L-alanine
-
 ?
L-kynurenine + H2O
-
 Pseudomonas fluorescens anthranilate + L-alanine
-
 ?
additional information 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 Pseudomonas fluorescens ?
-
 ?
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 Homo sapiens ?
-
 ?

Synonyms

Synonyms Comment Organism
HsKynase
-
 Homo sapiens
PfKynase
-
 Pseudomonas fluorescens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Homo sapiens
37
-
 assay at Pseudomonas fluorescens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.23
-
 L-kynurenine pH 8.0, 37°C, recombinant enzyme Homo sapiens
0.23
-
 3-fluoro-DL-kynurenine pH 8.0, 37°C, recombinant enzyme Homo sapiens
0.23
-
 3,5-dibromo-L-kynurenine pH 8.0, 37°C, recombinant enzyme Pseudomonas fluorescens
0.33
-
 3-methyl-DL-kynurenine pH 8.0, 37°C, recombinant enzyme Homo sapiens
0.47
-
 5-chloro-L-kynurenine pH 8.0, 37°C, recombinant enzyme Homo sapiens
0.63
-
 5-bromo-L-kynurenine pH 8.0, 37°C, recombinant enzyme Homo sapiens
0.67
-
 3-chloro-DL-kynurenine pH 8.0, 37°C, recombinant enzyme Homo sapiens
0.71
-
 3-chloro-DL-kynurenine pH 8.0, 37°C, recombinant enzyme Pseudomonas fluorescens
1
-
 3-hydroxy-L-kynurenine pH 8.0, 37°C, recombinant enzyme Pseudomonas fluorescens
1.2
-
 3,5-dibromo-L-kynurenine pH 8.0, 37°C, recombinant enzyme Homo sapiens
1.3
-
 5-bromo-3-chloro-DL-kynurenine pH 8.0, 37°C, recombinant enzyme Homo sapiens
1.5
-
 3-methyl-DL-kynurenine pH 8.0, 37°C, recombinant enzyme Pseudomonas fluorescens
1.9
-
 3-bromo-L-kynurenine pH 8.0, 37°C, recombinant enzyme Homo sapiens
3.5
-
 3-hydroxy-L-kynurenine pH 8.0, 37°C, recombinant enzyme Homo sapiens
6.3
-
 5-bromo-3-chloro-DL-kynurenine pH 8.0, 37°C, recombinant enzyme Pseudomonas fluorescens
6.9
-
 3-fluoro-DL-kynurenine pH 8.0, 37°C, recombinant enzyme Pseudomonas fluorescens
8.7
-
 5-chloro-L-kynurenine pH 8.0, 37°C, recombinant enzyme Pseudomonas fluorescens
11
-
 3-bromo-L-kynurenine pH 8.0, 37°C, recombinant enzyme Pseudomonas fluorescens
11.9
-
 5-bromo-L-kynurenine pH 8.0, 37°C, recombinant enzyme Pseudomonas fluorescens
16
-
 L-kynurenine pH 8.0, 37°C, recombinant enzyme Pseudomonas fluorescens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
 assay at Homo sapiens
8
-
 assay at Pseudomonas fluorescens

Cofactor

Cofactor Comment Organism Structure
pyridoxal 5'-phosphate dependent on Homo sapiens
pyridoxal 5'-phosphate dependent on Pseudomonas fluorescens

General Information

General Information Comment Organism
metabolism the enzyme is a key enzyme in the kynurenine pathway of tryptophan catabolism in both bacteria and animals, and catalyzes the unique beta,gamma-cleavage of aryl substituted gamma-keto-alpha-amino acids Homo sapiens
metabolism the enzyme is a key enzyme in the kynurenine pathway of tryptophan catabolism in both bacteria and animals, and catalyzes the unique beta,gamma-cleavage of aryl substituted gamma-keto-alpha-amino acids Pseudomonas fluorescens
additional information modeling of 3,5-dibromo-L-kynurenine in the active site of the human enzyme Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.465
-
 L-kynurenine pH 8.0, 37°C, recombinant enzyme Homo sapiens
1.1
-
 5-chloro-L-kynurenine pH 8.0, 37°C, recombinant enzyme Homo sapiens
1.5
-
 5-bromo-L-kynurenine pH 8.0, 37°C, recombinant enzyme Homo sapiens
1.8
-
 3-methyl-DL-kynurenine pH 8.0, 37°C, recombinant enzyme Homo sapiens
2.5
-
 3-hydroxy-L-kynurenine pH 8.0, 37°C, recombinant enzyme Pseudomonas fluorescens
2.7
-
 3-fluoro-DL-kynurenine pH 8.0, 37°C, recombinant enzyme Homo sapiens
4.4
-
 3-bromo-L-kynurenine pH 8.0, 37°C, recombinant enzyme Homo sapiens
5.5
-
 3-bromo-L-kynurenine pH 8.0, 37°C, recombinant enzyme Pseudomonas fluorescens
6.5
-
 5-bromo-3-chloro-DL-kynurenine pH 8.0, 37°C, recombinant enzyme Homo sapiens
7.9
-
 3,5-dibromo-L-kynurenine pH 8.0, 37°C, recombinant enzyme Homo sapiens
8.2
-
 3-chloro-DL-kynurenine pH 8.0, 37°C, recombinant enzyme Homo sapiens
11
-
 3-chloro-DL-kynurenine pH 8.0, 37°C, recombinant enzyme Pseudomonas fluorescens
21
-
 3,5-dibromo-L-kynurenine pH 8.0, 37°C, recombinant enzyme Pseudomonas fluorescens
22
-
 3-methyl-DL-kynurenine pH 8.0, 37°C, recombinant enzyme Pseudomonas fluorescens
22
-
 5-bromo-3-chloro-DL-kynurenine pH 8.0, 37°C, recombinant enzyme Pseudomonas fluorescens
90
-
 3-fluoro-DL-kynurenine pH 8.0, 37°C, recombinant enzyme Pseudomonas fluorescens
123
-
 3-hydroxy-L-kynurenine pH 8.0, 37°C, recombinant enzyme Homo sapiens
600
-
 L-kynurenine pH 8.0, 37°C, recombinant enzyme Pseudomonas fluorescens
1800
-
 5-chloro-L-kynurenine pH 8.0, 37°C, recombinant enzyme Pseudomonas fluorescens
3300
-
 5-bromo-L-kynurenine pH 8.0, 37°C, recombinant enzyme Pseudomonas fluorescens