Application | Comment | Organism |
---|---|---|
medicine | KMO and its enzymatic product QUIN are potential broad-spectrum antiviral factor therapeutics against emerging pathogenic viruses | Mus musculus |
Cloned (Comment) | Organism |
---|---|
gene kmo, KMO is an interferon-dependent gene, quantitative RT-PCR enzyme expression analysis | Mus musculus |
Protein Variants | Comment | Organism |
---|---|---|
E366A | site-directed mutagenesis, mutation of a catalytic residue, inactive mutant | Mus musculus |
additional information | the KMO expression is effectively inhibited using small interfering RNA (siRNA) and short hairpin RNA (shRNA), respectively. HSV-1 replication is significantly enhanced in KMO-knockdown cells compared to wild-type cells. Overexpression of catalytically inactive KMO catalytic residues mutants has no significant inhibition effect on HSV-1 infection | Mus musculus |
Y194A | site-directed mutagenesis, mutation of a catalytic residue, inactive mutant | Mus musculus |
Y99A | site-directed mutagenesis, mutation of a catalytic residue, inactive mutant | Mus musculus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
L-kynurenine + NADPH + H+ + O2 | Mus musculus | - |
3-hydroxy-L-kynurenine + NADP+ + H2O | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mus musculus | Q91WN4 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
RAW-264.7 cell | - |
Mus musculus | - |
WT-J2-BMM cell | wild-type bone-marrow-derived macrophage cells | Mus musculus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
L-kynurenine + NADPH + H+ + O2 | - |
Mus musculus | 3-hydroxy-L-kynurenine + NADP+ + H2O | - |
? |
Synonyms | Comment | Organism |
---|---|---|
KMO | - |
Mus musculus |
kynurenine-3-monooxygenase | - |
Mus musculus |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
FAD | - |
Mus musculus | |
NADPH | - |
Mus musculus |
Organism | Comment | Expression |
---|---|---|
Mus musculus | upregulation of KMO expression is abrogated in the IFN-I receptor (IFNAR) deficient (Ifnar-/-)-J2-BMMs | down |
Mus musculus | KMO is an interferon-inducible gene. KMO expression was significantly induced by IFN-alpha stimulation in Raw264.7 and WT-J2-BMM cells. The upregulation of KMO expression is abrogated in the IFN-I receptor (IFNAR) deficient (Ifnar-/-)-J2-BMMs. KMO expression is significantly elevated by HSV-1 infection in both dose-dependent and time-dependent in Raw-264.7 cells | up |
General Information | Comment | Organism |
---|---|---|
malfunction | kmo-/- mice are vulnerable to pathogenic viral challenge with severe clinical symptoms. HSV-1 replication is significantly enhanced in KMO-knockdown cells compared to wild-type cells. Mutant kmo-/- mice are more susceptible to viral infections | Mus musculus |
metabolism | kynurenine-3-monooxygenase (KMO) is a key rate-limiting enzyme in the kynurenine pathway (KP) in tryptophan metabolism. The tryptophan (Trp) metabolism through the kynurenine pathway (KP) is well known to play a critical function in cancer, autoimmune and neurodegenerative diseases | Mus musculus |
additional information | residues Tyr 99, Tyr 194, and Glu 366 are critical to the enzymatic activity of KMO | Mus musculus |
physiological function | kynurenine-3-monooxygenase (KMO) broadly inhibits viral infections via triggering NMDAR/Ca2+ influx and CaMKII/IRF3-mediated IFN-beta production. Kynurenine-3-monooxygenase (KMO), a key rate-limiting enzyme in the kynurenine pathway (KP), and quinolinic acid (QUIN), a key enzymatic product of KMO enzyme, exerts an antiviral function against a broad range of viruses. The enzymatic activity of KMO is required for its antiviral function, it is a key antiviral factor physiologically involved in modulating antiviral immunity. The supernatants from KMO-treated cells significantly inhibits HSV-1 infection in Vero cells and 293T cells. Mechanistically, QUIN induces the production of type I interferon (IFN-I) via activating the N-methyl-D-aspartate receptor (NMDAR) and Ca2+ influx to activate the calcium/calmodulin-dependent protein kinase II (CaMKII)/interferon regulatory factor 3 (IRF3). QUIN treatment effectively inhibits viral infections and alleviates disease progression in mice, detailed mechanism overview | Mus musculus |