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Literature summary extracted from
- Biochemistry and structural studies of kynurenine 3-monooxygenase reveal allosteric inhibition by Ro 61-8048 (2017), FASEB J., 32, 2036-2045.
Application
| EC Number | Application | Comment | Organism |
|---|---|---|---|
| 1.14.13.9 | medicine | the enzyme is a potential therapeutic target for neurodegenerative and neurologic disorders | Homo sapiens |
Cloned(Commentary)
| EC Number | Cloned (Comment) | Organism |
|---|---|---|
| 1.14.13.9 | expression in Escherichia coli and in HEK293T cells | Homo sapiens |
Crystallization (Commentary)
| EC Number | Crystallization (Comment) | Organism |
|---|---|---|
| 1.14.13.9 | crystals are obtained by hanging-drop vapor diffusion at 20°C. Crystal structures of the complex of the full-length enzyme with the substrate L-kynurenine and in complex with L-kynurenine and Ro 61-8048 at a resolution of 1.85 and 2.34 A, respectively. The crystals of the enzyme-L-kynurenine complex belong to the space group P2(1) with 1 enzyme molecule in the asymmetric unit. The crystal structure of the enzymeL-kynurenine-Ro61-8048 complex belongs to the space group P2(1)2(1)2(1) with 1 pfKMO molecule in the asymmetric unit. The crystal structure of the SeMet enzyme derivative belongs to the space group P2(1) with 2 enzyme molecules in the asymmetric unit | Pseudomonas fluorescens |
Protein Variants
| EC Number | Protein Variants | Comment | Organism |
|---|---|---|---|
| 1.14.13.9 | E366Q | 2% of the enzyme activity compared with that of the wild-type enzyme | Homo sapiens |
| 1.14.13.9 | E372A | about 15% of the enzyme activity compared with that of the wild-type enzyme | Pseudomonas fluorescens |
| 1.14.13.9 | E372Q | about 5% of the enzyme activity compared with that of the wild-type enzyme | Pseudomonas fluorescens |
| 1.14.13.9 | M367A | 2% of the enzyme activity compared with that of the wild-type enzyme | Homo sapiens |
| 1.14.13.9 | M367L | 13% of the enzyme activity compared with that of the wild-type enzyme | Homo sapiens |
| 1.14.13.9 | M373A | no activity detected | Pseudomonas fluorescens |
| 1.14.13.9 | M373L | about 60% of the enzyme activity compared with that of the wild-type enzyme | Pseudomonas fluorescens |
| 1.14.13.9 | additional information | the enzyme is systematically truncated according to the sequence alignments and the predicted secondary structures. For the truncations 1-377, 1-379, and 1-394, which have 1 or 2 more predicted alpha-helices than that of the 1-372/374, no or weak protein expression is detected. Although for the truncation 1-430 that has the C-terminal hydrophobic tail removed, no enzymatic activities can be detected but the protein expression is normal. The results indicate that the C-terminal portion is important for both the folding and the enzymatic activity | Homo sapiens |
| 1.14.13.9 | N363A | 28% of the enzyme activity compared with that of the wild-type enzyme | Homo sapiens |
| 1.14.13.9 | N363D | no activity detected | Homo sapiens |
| 1.14.13.9 | N369A | about 65% of the enzyme activity compared with that of the wild-type enzyme | Pseudomonas fluorescens |
| 1.14.13.9 | N369D | no activity detected | Pseudomonas fluorescens |
| 1.14.13.9 | N465A | about 80% of the enzyme activity compared with that of the wild-type enzyme | Homo sapiens |
| 1.14.13.9 | Q424A | mutation does not greatly affect enzyme activity. Ro 61-8048 shows no inhibition to the pfKMO mutant enzyme | Pseudomonas fluorescens |
| 1.14.13.9 | R84A | no activity detected | Pseudomonas fluorescens |
| 1.14.13.9 | R85A | no activity detected | Homo sapiens |
| 1.14.13.9 | R85K | 1% of the enzyme activity compared with that of the wild-type enzyme | Homo sapiens |
| 1.14.13.9 | Y398A | 1% of the enzyme activity compared with that of the wild-type enzyme | Homo sapiens |
| 1.14.13.9 | Y398F | 1% of the enzyme activity compared with that of the wild-type enzyme | Homo sapiens |
| 1.14.13.9 | Y404A | no activity detected | Pseudomonas fluorescens |
| 1.14.13.9 | Y404F | about 40% of the enzyme activity compared with that of the wild-type enzyme | Pseudomonas fluorescens |
| 1.14.13.9 | Y98A | no activity detected | Pseudomonas fluorescens |
| 1.14.13.9 | Y98F | about 1% of the enzyme activity compared with that of the wild-type enzyme | Pseudomonas fluorescens |
| 1.14.13.9 | Y99A | no activity detected | Homo sapiens |
| 1.14.13.9 | Y99F | 7% of the enzyme activity compared with that of the wild-type enzyme | Homo sapiens |
Inhibitors
| EC Number | Inhibitors | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.14.13.9 | Ro 61-8048 | allosteric | Homo sapiens |  |
| 1.14.13.9 | Ro 61-8048 | noncompetitive. Theinhibitor is bound in the tunnel at the interface where the N- and C-terminal domains associate | Pseudomonas fluorescens | |
Molecular Weight [Da]
| EC Number | Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|---|
| 1.14.13.9 | 60386 | - |
calculated from sequence | Homo sapiens |
| 1.14.13.9 | 62136 | - |
native mass spectrum analysis | Homo sapiens |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 1.14.13.9 | Homo sapiens | O15229 | - |
- |
| 1.14.13.9 | Pseudomonas fluorescens | Q84HF5 | - |
- |
Posttranslational Modification
| EC Number | Posttranslational Modification | Comment | Organism |
|---|---|---|---|
| 1.14.13.9 | glycoprotein | glycosylation has only a marginal effect on enzyme activity | Homo sapiens |
Purification (Commentary)
| EC Number | Purification (Comment) | Organism |
|---|---|---|
| 1.14.13.9 | - |
Pseudomonas fluorescens |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.14.13.9 | L-kynurenine + NADPH + H+ + O2 | - |
Pseudomonas fluorescens | 3-hydroxy-L-kynurenine + NADP+ + H2O | - |
? | |
| 1.14.13.9 | L-kynurenine + NADPH + H+ + O2 | - |
Homo sapiens | 3-hydroxy-L-kynurenine + NADP+ + H2O | - |
? | |
Temperature Optimum [°C]
| EC Number | Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|---|
| 1.14.13.9 | 37 | - |
assay at | Pseudomonas fluorescens |
| 1.14.13.9 | 37 | - |
assay at | Homo sapiens |
pH Optimum
| EC Number | pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|---|
| 1.14.13.9 | 8 | - |
assay at | Pseudomonas fluorescens |
| 1.14.13.9 | 8 | - |
assay at | Homo sapiens |
Ki Value [mM]
| EC Number | Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|---|
| 1.14.13.9 | 0.0135 | - |
Ro 61-8048 | pH and temperature not specified in the publication | Pseudomonas fluorescens | |
General Information
| EC Number | General Information | Comment | Organism |
|---|---|---|---|
| 1.14.13.9 | drug target | the enzyme is a potential therapeutic target for neurodegenerative and neurologic disorders | Homo sapiens |
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