| kynurenine 3-monooxygenase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Structure of the kynurenine 3-monooxygenase dimer, generated from 4J34.[1] One monomer is depicted in cartoon format (cyan) and the second monomer is displayed in ribbon format (green). The flexible linker regions (residues 96-104) are colored red. Flavin adenine dinucleotide (FAD) is shown as spheres color-coded according to atom type. | |||||||||
| Identifiers | |||||||||
| EC no. | 1.14.13.9 | ||||||||
| CAS no. | 9029-61-2 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / QuickGO | ||||||||
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In enzymology, a kynurenine 3-monooxygenase (EC 1.14.13.9) is an enzyme that catalyzes the chemical reaction
- L-kynurenine + NADPH + H+ + O2 ⇌ 3-hydroxy-L-kynurenine + NADP+ + H2O
Kynurenine 3-monooxygenase is the expression product of the KMO (gene). The systematic name of this enzyme class is L-kynurenine, NADPH:oxygen oxidoreductase (3-hydroxylating). Other names in common use include kynurenine 3-hydroxylase, kynurenine hydroxylase, and L-kynurenine-3-hydroxylase. It participates in tryptophan metabolism through the kynurenine catabolic pathway. This enzyme belongs to the family of oxidoreductases, to be specific, those acting on paired donors, with O2 as the oxidant. Kynurenine 3-monooxygenase catalyzes the insertion of molecular oxygen into the aromatic ring of kynurenine to produce 3-hydroxy-L-kynurenine.[2] It employs one cofactor, FAD. Kynurenine 3-monooxygenase serves as an important branch point in the kynurenine pathway and, as a result, is an attractive drug target for immunological, neurodegenerative, and neuroinflammatory diseases.[3] Currently, most research on the kynurenine 3-monooxygenase enzyme has been focused primarily on rat models[4] and in yeast,[5] both of which have been demonstrated to have high sequence homology with the human kynurenine 3-monooxygenase protein. Studies have shown the beneficial effects of enzyme inhibition in these eukaryotic kynurenine 3-monooxygenase active sites, thus making this enzyme an attractive target for human drug design.[3][5]
- ^ Amaral, M. (2014). "Crystal Structure of kynurenine 3-monooxygenase – truncated at position 394 plus HIS tag cleaved". doi:10.2210/pdb4j34/pdb.
{{cite journal}}: Cite journal requires|journal=(help) - ^ Filippini, Graziella Allegri; Costa, Carlo V. L.; Bertazzo, Antonella; International Meeting on Tryptophan Research (1998). Recent advances in tryptophan research : tryptophan and serotonin pathways. Advances in Experimental Medicine and Biology. Vol. 398. doi:10.1007/978-1-4613-0381-7. ISBN 978-1-4613-8026-9. S2CID 38080353.
- ^ a b Smith, Jason R.; Jamie, Joanne F.; Guillemin, Gilles J. (February 2016). "Kynurenine-3-monooxygenase: a review of structure, mechanism, and inhibitors". Drug Discovery Today. 21 (2): 315–324. doi:10.1016/j.drudis.2015.11.001. ISSN 1359-6446. PMID 26589832.
- ^ Horn, U.; Ullrich, V.; Staudinger, H.J (1971). "Purification and characterization of L-kynurenine 3-hydroxylase (EC 1.14.1.2.) from rat liver". Hoppe-Seyler's Z. Physiol. Chem. 352 (6): 837–842. doi:10.1515/bchm2.1971.352.1.837. PMID 5087636.
- ^ a b Amaral, M; Levy, C; Heyes, DJ; Lafite, P; Outeiro, TF; Giorgini, F; Leys, D; Scrutton, NS (2013). "Structural basis of kynurenine 3-monooxygenase inhibition". Nature. 496 (7445): 382–385. Bibcode:2013Natur.496..382A. doi:10.1038/nature12039. PMC 3736096. PMID 23575632.