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Literature summary for 1.14.13.9 extracted from

  • Zhao, J.; Chen, J.; Wang, C.; Liu, Y.; Li, M.; Li, Y.; Li, R.; Han, Z.; Wang, J.; Chen, L.; Shu, Y.; Cheng, G.; Sun, C.
    Kynurenine-3-monooxygenase (KMO) broadly inhibits viral infections via triggering NMDAR/Ca2+ influx and CaMKII/IRF3-mediated IFN-beta production (2022), PLoS Pathog., 18, e1010366 .
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
medicine KMO and its enzymatic product QUIN are potential broad-spectrum antiviral factor therapeutics against emerging pathogenic viruses Mus musculus

Cloned(Commentary)

Cloned (Comment) Organism
gene kmo, KMO is an interferon-dependent gene, quantitative RT-PCR enzyme expression analysis Mus musculus

Protein Variants

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/ Products (Substrates)

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

Organism UniProt Comment Textmining
Mus musculus Q91WN4
-
-

Source Tissue

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 and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-kynurenine + NADPH + H+ + O2
-
Mus musculus 3-hydroxy-L-kynurenine + NADP+ + H2O
-
?

Synonyms

Synonyms Comment Organism
KMO
-
Mus musculus
kynurenine-3-monooxygenase
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Mus musculus

Cofactor

Cofactor Comment Organism Structure
FAD
-
Mus musculus
NADPH
-
Mus musculus

Expression

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

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