EC Number | Application | Comment | Organism |
---|---|---|---|
1.14.13.9 | drug development | enzyme KMO is an important drug target due to its role in regulating the levels of bioactive substances with contrasting effects. For treatment of central nervous related diseases, it is required that enzyme inhibitors should be both blood brain barrier permeable and should not cause hydrogen peroxide as a harmful side product. Molecular dynamics simulations and MM/GBSA calculations, overview | Saccharomyces cerevisiae |
1.14.13.9 | drug development | enzyme KMO is an important drug target due to its role in regulating the levels of bioactive substances with contrasting effects. For treatment of central nervous related diseases, it is required that enzyme inhibitors should be both blood brain barrier permeable and should not cause hydrogen peroxide as a harmful side product. Molecular dynamics simulations and MM/GBSA calculations, overview | Pseudomonas fluorescens |
1.14.13.9 | drug development | enzyme KMO is an important drug target due to its role in regulating the levels of bioactive substances with contrasting effects. For treatment of central nervous related diseases, it is required that enzyme inhibitors should be both blood brain barrier permeable and should not cause hydrogen peroxide as a harmful side product. Molecular dynamics simulations and MM/GBSA calculations, overview | Homo sapiens |
EC Number | Protein Variants | Comment | Organism |
---|---|---|---|
1.14.13.9 | additional information | generation of a C-terminal domain truncated human KMO whose membrane targeting sequence in its C-terminal domain is suggested to be an essential part of its catalysis | Saccharomyces cerevisiae |
1.14.13.9 | additional information | generation of a C-terminal domain truncated human KMO whose membrane targeting sequence in its C-terminal domain is suggested to be an essential part of its catalysis | Pseudomonas fluorescens |
1.14.13.9 | additional information | generation of a C-terminal domain truncated human KMO whose membrane targeting sequence in its C-terminal domain is suggested to be an essential part of its catalysis | Homo sapiens |
EC Number | Inhibitors | Comment | Organism | Structure |
---|---|---|---|---|
1.14.13.9 | 3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide | Ro 61-8048 | Homo sapiens | |
1.14.13.9 | 3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide | Ro 61-8048, different binding modes of the inhibitor Ro 61-8048 in scKMO and in pfKMO, overview | Pseudomonas fluorescens | |
1.14.13.9 | 3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide | Ro 61-8048, different binding modes of the inhibitor Ro 61-8048 in scKMO and in pfKMO, overview. Ro 61-8048-scKMO complex structure analysis | Saccharomyces cerevisiae | |
1.14.13.9 | CHDI-340246 | CHDI-340246-scKMO complex structure analysis | Saccharomyces cerevisiae | |
1.14.13.9 | Cl- | low concentrations of NaCl solution stabilize the enzyme and decrease the limiting rate of reduction by 30fold. This effect is specific to the Cl- anion. The rate of hydroxylation is also moderately reduced with the introduction of NaCl solution | Pseudomonas fluorescens | |
1.14.13.9 | additional information | enzyme structure and ligand interaction analysis using the crystal structure of hKMO (PDB ID 5X68), library screening from Zinc15 database, detailed overview | Homo sapiens | |
1.14.13.9 | additional information | enzyme structure and ligand interaction analysis using the crystal structure of pfKMO (PDB ID 5NAK), library screening from Zinc15 database, detailed overview | Pseudomonas fluorescens | |
1.14.13.9 | additional information | enzyme structure and ligand interaction analysis using the crystal structure of scKMO (PDB ID 4J34), library screening from Zinc15 database, detailed overview | Saccharomyces cerevisiae | |
1.14.13.9 | ZINC19827377 | the inhibitor does not cause hydrogen peroxide as a harmful side product | Homo sapiens | |
1.14.13.9 | ZINC19827377 | - |
Pseudomonas fluorescens | |
1.14.13.9 | ZINC19827377 | - |
Saccharomyces cerevisiae | |
1.14.13.9 | ZINC71915355 | the inhibitor is both blood brain barrier permeable and does not cause hydrogen peroxide as a harmful side product | Homo sapiens | |
1.14.13.9 | ZINC71915355 | - |
Pseudomonas fluorescens | |
1.14.13.9 | ZINC71915355 | - |
Saccharomyces cerevisiae |
EC Number | Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|---|
1.14.13.9 | mitochondrial outer membrane | - |
Homo sapiens | 5741 | - |
EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|---|
1.14.13.9 | L-kynurenine + NADPH + H+ + O2 | Saccharomyces cerevisiae | - |
3-hydroxy-L-kynurenine + NADP+ + H2O | - |
? | |
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 | - |
? |
EC Number | Organism | UniProt | Comment | Textmining |
---|---|---|---|---|
1.14.13.9 | Homo sapiens | O15229 | - |
- |
1.14.13.9 | Pseudomonas fluorescens | Q84HF5 | - |
- |
1.14.13.9 | Saccharomyces cerevisiae | P38169 | - |
- |
EC Number | Reaction | Comment | Organism | Reaction ID |
---|---|---|---|---|
1.14.13.9 | L-kynurenine + NADPH + H+ + O2 = 3-hydroxy-L-kynurenine + NADP+ + H2O | the mechanism of L-Kyn catalysis by KMO is composed of reductive and oxidative half reactions. The binding of the substrate induces the reduction of FAD by NADH or by NADPH | Saccharomyces cerevisiae | |
1.14.13.9 | L-kynurenine + NADPH + H+ + O2 = 3-hydroxy-L-kynurenine + NADP+ + H2O | the mechanism of L-Kyn catalysis by KMO is composed of reductive and oxidative half reactions. The binding of the substrate induces the reduction of FAD by NADH or by NADPH | Pseudomonas fluorescens | |
1.14.13.9 | L-kynurenine + NADPH + H+ + O2 = 3-hydroxy-L-kynurenine + NADP+ + H2O | the mechanism of L-Kyn catalysis by KMO is composed of reductive and oxidative half reactions. The binding of the substrate induces the reduction of FAD by NADH or by NADPH | Homo sapiens |
EC Number | Source Tissue | Comment | Organism | Textmining |
---|---|---|---|---|
1.14.13.9 | central nervous system | - |
Homo sapiens | - |
EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|---|
1.14.13.9 | L-kynurenine + NADPH + H+ + O2 | - |
Saccharomyces cerevisiae | 3-hydroxy-L-kynurenine + NADP+ + H2O | - |
? | |
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 | - |
? | |
1.14.13.9 | additional information | the mechanism of L-Kyn catalysis by KMO is composed of reductive and oxidative half reactions. The binding of the substrate induces the reduction of FAD by NADH or by NADPH. The initiation of FAD reduction is not unique to the substrate binding. It is also observed upon the binding of several inhibitors. The molecules that induce reduction of FAD other than the substrate are named as non-substrate effectors, e.g. GSK180 and Ro 61-8048 for enzyme pfKMO. Since the non-substrate effectors eliminate the hydroxyl transfer event but nonetheless initiate the formation of the FAD-hydroperoxide intermediate, they cause hydrogen peroxide formation. The triggering factor can arise from the substrate induced conformational changes in the loop above the isoalloxazine ring system | Pseudomonas fluorescens | ? | - |
- |
|
1.14.13.9 | additional information | the mechanism of L-Kyn catalysis by KMO is composed of reductive and oxidative half reactions. The binding of the substrate induces the reduction of FAD by NADH or by NADPH. The initiation of FAD reduction is not unique to the substrate binding. It is also observed upon the binding of several inhibitors. The molecules that induce reduction of FAD other than the substrate are named as non-substrate effectors, e.g. UPF-648 for enzyme scKMO. Since the non-substrate effectors eliminate the hydroxyl transfer event but nonetheless initiate the formation of the FAD-hydroperoxide intermediate, they cause hydrogen peroxide formation. The triggering factor can arise from the substrate induced conformational changes in the loop above the isoalloxazine ring system | Saccharomyces cerevisiae | ? | - |
- |
|
1.14.13.9 | additional information | the mechanism of L-Kyn catalysis by KMO is composed of reductive and oxidative half reactions. The binding of the substrate induces the reduction of FAD by NADH or by NADPH. The initiation of FAD reduction is not unique to the substrate binding. It is also observed upon the binding of several inhibitors. The molecules that induce reduction of FAD other than the substrate are named as non-substrate effectors. Since the non-substrate effectors eliminate the hydroxyl transfer event but nonetheless initiate the formation of the FAD-hydroperoxide intermediate, they cause hydrogen peroxide formation. The triggering factor can arise from the substrate induced conformational changes in the loop above the isoalloxazine ring system | Homo sapiens | ? | - |
- |
EC Number | Subunits | Comment | Organism |
---|---|---|---|
1.14.13.9 | More | the structure of KMO can be realized as three domains: the first domain is where FAD is buried within beta-sheets and alpha-helices, one of which is the long alpha-helix that leads to the C-terminal domain. This helix and a loop that stands above the isoalloxazine rings of FAD define the borders of the active site in this region. The second region contains the residues of alpha-helices and beta-sheets whose side chains set the final border to the active site. Therefore, the active site is contained at the interface of the first and second regions. The third region of PfKMO consists of four alpha-helices while in scKMO and hKMO there are only the two alpha-helices of the transmembrane domain | Saccharomyces cerevisiae |
1.14.13.9 | More | the structure of KMO can be realized as three domains: the first domain is where FAD is buried within beta-sheets and alpha-helices, one of which is the long alpha-helix that leads to the C-terminal domain. This helix and a loop that stands above the isoalloxazine rings of FAD define the borders of the active site in this region. The second region contains the residues of alpha-helices and beta-sheets whose side chains set the final border to the active site. Therefore, the active site is contained at the interface of the first and second regions. The third region of PfKMO consists of four alpha-helices while in scKMO and hKMO there are only the two alpha-helices of the transmembrane domain | Pseudomonas fluorescens |
1.14.13.9 | More | the structure of KMO can be realized as three domains: the first domain is where FAD is buried within beta-sheets and alpha-helices, one of which is the long alpha-helix that leads to the C-terminal domain. This helix and a loop that stands above the isoalloxazine rings of FAD define the borders of the active site in this region. The second region contains the residues of alpha-helices and beta-sheets whose side chains set the final border to the active site. Therefore, the active site is contained at the interface of the first and second regions. The third region of PfKMO consists of four alpha-helices while in scKMO and hKMO there are only the two alpha-helices of the transmembrane domain | Homo sapiens |
EC Number | Synonyms | Comment | Organism |
---|---|---|---|
1.14.13.9 | FAD dependent kynurenine 3-monooxygenase | - |
Saccharomyces cerevisiae |
1.14.13.9 | FAD dependent kynurenine 3-monooxygenase | - |
Pseudomonas fluorescens |
1.14.13.9 | FAD dependent kynurenine 3-monooxygenase | - |
Homo sapiens |
1.14.13.9 | flavin adenine dinucleotide dependent kynurenine 3-monooxygenase | - |
Saccharomyces cerevisiae |
1.14.13.9 | flavin adenine dinucleotide dependent kynurenine 3-monooxygenase | - |
Pseudomonas fluorescens |
1.14.13.9 | flavin adenine dinucleotide dependent kynurenine 3-monooxygenase | - |
Homo sapiens |
1.14.13.9 | hKMO | - |
Homo sapiens |
1.14.13.9 | KMO | - |
Saccharomyces cerevisiae |
1.14.13.9 | KMO | - |
Pseudomonas fluorescens |
1.14.13.9 | KMO | - |
Homo sapiens |
1.14.13.9 | pfKMO | - |
Pseudomonas fluorescens |
1.14.13.9 | scKMO | - |
Saccharomyces cerevisiae |
EC Number | Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|---|
1.14.13.9 | 37 | - |
assay at | Homo sapiens |
EC Number | pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|---|
1.14.13.9 | 7.4 | - |
assay at | Homo sapiens |
EC Number | Cofactor | Comment | Organism | Structure |
---|---|---|---|---|
1.14.13.9 | FAD | - |
Saccharomyces cerevisiae | |
1.14.13.9 | FAD | - |
Pseudomonas fluorescens | |
1.14.13.9 | FAD | - |
Homo sapiens | |
1.14.13.9 | NADPH | - |
Saccharomyces cerevisiae | |
1.14.13.9 | NADPH | - |
Pseudomonas fluorescens | |
1.14.13.9 | NADPH | - |
Homo sapiens |
EC Number | General Information | Comment | Organism |
---|---|---|---|
1.14.13.9 | malfunction | hKMO is inactive without its membrane targeting domain | Homo sapiens |
1.14.13.9 | metabolism | FAD-dependent kynurenine 3-monooxygenase (KMO) catalyzes the conversion of L-kynurenine (L-Kyn) to 3-Hydroxykynurenine (3-HK) in the kynurenine pathway. In the pathway responsible for the catabolism of tryptophan, enzyme KMO regulates the levels of bioactive substances. L-Kyn, is also a substrate to both kynureninase (KYNU) and especially to kynurenine aminotransferase (KAT), which converts L-Kyn to kynurenic acid (KynA), a neuroprotective agent for being the antagonist of NMDA, alpha-7 nicotinic acetylcholine, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate, and an antioxidant for being the scavenger of several free radical species | Saccharomyces cerevisiae |
1.14.13.9 | metabolism | FAD-dependent kynurenine 3-monooxygenase (KMO) catalyzes the conversion of L-kynurenine (L-Kyn) to 3-Hydroxykynurenine (3-HK) in the kynurenine pathway. In the pathway responsible for the catabolism of tryptophan, enzyme KMO regulates the levels of bioactive substances. L-Kyn, is also a substrate to both kynureninase (KYNU) and especially to kynurenine aminotransferase (KAT), which converts L-Kyn to kynurenic acid (KynA), a neuroprotective agent for being the antagonist of NMDA, alpha-7 nicotinic acetylcholine, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate, and an antioxidant for being the scavenger of several free radical species | Homo sapiens |
1.14.13.9 | metabolism | FAD-dependent kynurenine 3-monooxygenase (KMO) catalyzes the conversion of L-kynurenine (L-Kyn) to 3-Hydroxykynurenine (3-HK) in the kynurenine pathway. In the pathway responsible for the catabolism of tryptophan, enzyme KMO regulates the levels of bioactive substances. L-Kyn, is also a substrate to both kynureninase (KYNU) and especially to kynurenine aminotransferase (KAT), which converts L-Kyn to kynurenic acid (KynA); a neuroprotective agent for being the antagonist of NMDA, alpha-7 nicotinic acetylcholine, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate, and an antioxidant for being the scavenger of several free radical species | Pseudomonas fluorescens |
1.14.13.9 | additional information | PfKMO is active without its membrane targeting domain, structure comparisons with the enzymes from Saccharomyces cerevisiae and Homo sapiens, overview | Pseudomonas fluorescens |
1.14.13.9 | additional information | ScKMO is active without its membrane targeting domain, structure comparisons with the enzymes from Homo sapiens (hKMO) and Pseudomonas fluorescens (pfKMO), overview | Saccharomyces cerevisiae |
1.14.13.9 | additional information | structure comparisons with the enzymes from Saccharomyces cerevisiae (scKMO) and Pseudomonas fluorescens (pfKMO), overview | Homo sapiens |
1.14.13.9 | physiological function | kynurenine 3-monooxygenase (KMO) regulates the levels of bioactive substances in the kynurenine pathway of tryptophan catabolism and its activity is tied to many diseases. The product of the enzyme reaction, 3-hydroxy-L-kynurenine (3-HK), is a neurotoxic agent that induces apoptosis and damages wide range of cell types. It is further converted to the free-radical generator 3-hydroxyanthranilate (3-HanA) which is then converted to the selective N-methyl-D-aspartate (NMDA) receptor agonist quinolinate | Saccharomyces cerevisiae |
1.14.13.9 | physiological function | kynurenine 3-monooxygenase (KMO) regulates the levels of bioactive substances in the kynurenine pathway of tryptophan catabolism and its activity is tied to many diseases. The product of the enzyme reaction, 3-hydroxy-L-kynurenine (3-HK), is a neurotoxic agent that induces apoptosis and damages wide range of cell types. It is further converted to the free-radical generator 3-hydroxyanthranilate (3-HanA) which is then converted to the selective N-methyl-D-aspartate (NMDA) receptor agonist quinolinate | Pseudomonas fluorescens |
1.14.13.9 | physiological function | kynurenine 3-monooxygenase (KMO) regulates the levels of bioactive substances in the kynurenine pathway of tryptophan catabolism and its activity is tied to many diseases. The product of the enzyme reaction, 3-hydroxy-L-kynurenine (3-HK), is a neurotoxic agent that induces apoptosis and damages wide range of cell types. It is further converted to the free-radical generator 3-hydroxyanthranilate (3-HanA) which is then converted to the selective N-methyl-D-aspartate (NMDA) receptor agonist quinolinate. High levels of these substances correlate with the neurodegenerative diseases (Huntington's, Alzheimer's, and Parkinson's) | Homo sapiens |