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Literature summary for 3.7.1.3 extracted from

  • Lima, S.; Kumar, S.; Gawandi, V.; Momany, C.; Phillips, R.S.
    Crystal structure of the Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex: insights into the molecular basis of kynureninase substrate specificity (2009), J. Med. Chem., 52, 389-396.
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
-
Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
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 Homo sapiens

Protein Variants

Protein Variants Comment Organism
H102W/N333T the mutant shows complete reversal of substrate specificity between 3-hydroxy-L-kynurenine and L-kynurenine Homo sapiens
H102W/S332G/N333T the mutant shows complete reversal of substrate specificity between 3-hydroxy-L-kynurenine and L-kynurenine Homo sapiens
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 Homo sapiens
S332G/N333T the mutant shows a very slight preference for L-kynurenine over 3-hydroxy-L-kynurenine Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
2-amino-4-[3'-hydroxyphenyl]-4-hydroxybutanoic acid most potent inhibitor Homo sapiens
3-hydroxyhippuric acid competitive inhibitor of kynureninase Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0283
-
3-hydroxy-L-kynurenine wild type enzyme, in 30 mM potassium phosphate, pH 8.0, and 0.04 mM pyridoxal 5'-phosphate, at 37°C Homo sapiens
0.2
-
3-hydroxy-L-kynurenine Km above 0.2 mM, mutant enzyme N333T, in 30 mM potassium phosphate, pH 8.0, and 0.04 mM pyridoxal 5'-phosphate, at 37°C Homo sapiens
0.327
-
L-kynurenine mutant enzyme H102W/N333T, in 30 mM potassium phosphate, pH 8.0, and 0.04 mM pyridoxal 5'-phosphate, at 37°C Homo sapiens
0.495
-
L-kynurenine wild type enzyme, in 30 mM potassium phosphate, pH 8.0, and 0.04 mM pyridoxal 5'-phosphate, at 37°C Homo sapiens
0.499
-
L-kynurenine mutant enzyme N333T, in 30 mM potassium phosphate, pH 8.0, and 0.04 mM pyridoxal 5'-phosphate, at 37°C Homo sapiens
0.51
-
L-kynurenine Km above 0.51 mM, mutant enzyme H102W/S332G/N333T, in 30 mM potassium phosphate, pH 8.0, and 0.04 mM pyridoxal 5'-phosphate, at 37°C Homo sapiens
0.51
-
3-hydroxy-L-kynurenine Km above 0.51 mM, mutant enzyme S332G/N333T, in 30 mM potassium phosphate, pH 8.0, and 0.04 mM pyridoxal 5'-phosphate, at 37°C Homo sapiens
0.54
-
L-kynurenine mutant enzyme S332G/N333T, in 30 mM potassium phosphate, pH 8.0, and 0.04 mM pyridoxal 5'-phosphate, at 37°C Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens Q16719
-
-

Purification (Commentary)

Purification (Comment) Organism
-
Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3-hydroxy-L-kynurenine + H2O preferred substrate Homo sapiens 3-hydroxyanthranilate + L-alanine
-
?
L-kynurenine + H2O
-
Homo sapiens anthranilate + L-alanine
-
?

Synonyms

Synonyms Comment Organism
Kynase
-
Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.0039
-
3-hydroxy-L-kynurenine kcat less than 0.0039 1/s, mutant enzyme N333T, in 30 mM potassium phosphate, pH 8.0, and 0.04 mM pyridoxal 5'-phosphate, at 37°C Homo sapiens
0.007
-
L-kynurenine mutant enzyme H102W/N333T, in 30 mM potassium phosphate, pH 8.0, and 0.04 mM pyridoxal 5'-phosphate, at 37°C Homo sapiens
0.0109
-
3-hydroxy-L-kynurenine kcat less than 0.0109 1/s, mutant enzyme S332G/N333T, in 30 mM potassium phosphate, pH 8.0, and 0.04 mM pyridoxal 5'-phosphate, at 37°C Homo sapiens
0.017
-
L-kynurenine mutant enzyme S332G/N333T, in 30 mM potassium phosphate, pH 8.0, and 0.04 mM pyridoxal 5'-phosphate, at 37°C Homo sapiens
0.018
-
L-kynurenine Km above 0.51 mM, mutant enzyme H102W/S332G/N333T, in 30 mM potassium phosphate, pH 8.0, and 0.04 mM pyridoxal 5'-phosphate, at 37°C Homo sapiens
0.026
-
L-kynurenine mutant enzyme N333T, in 30 mM potassium phosphate, pH 8.0, and 0.04 mM pyridoxal 5'-phosphate, at 37°C Homo sapiens
0.23
-
L-kynurenine wild type enzyme, in 30 mM potassium phosphate, pH 8.0, and 0.04 mM pyridoxal 5'-phosphate, at 37°C Homo sapiens
3.5
-
3-hydroxy-L-kynurenine wild type enzyme, in 30 mM potassium phosphate, pH 8.0, and 0.04 mM pyridoxal 5'-phosphate, at 37°C Homo sapiens

Cofactor

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