Kynurenine 3-monooxygenase

Definition:

Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn). Required for synthesis of quinolinic acid, a neurotoxic NMDA receptor antagonist and potential endogenous inhibitor of NMDA receptor signaling in axonal targeting, synaptogenesis and apoptosis during brain development. Quinolinic acid may also affect NMDA receptor signaling in pancreatic beta cells, osteoblasts, myocardial cells, and the gastrointestinal tract.

References:

[1]. Marta Amaral, et al. Structural basis of kynurenine 3-monooxygenase inhibition. Nature. 2013 Apr 18;496(7445):382-5. [Content Brief]

[2]. Trevor W Stone, et al. Endogenous kynurenines as targets for drug discovery and development. Nat Rev Drug Discov. 2002 Aug;1(8):609-20. [Content Brief]

[3]. Damian J Mole, et al. Kynurenine-3-monooxygenase inhibition prevents multiple organ failure in rodent models of acute pancreatitis. Nat Med. 2016 Feb;22(2):202-9. [Content Brief]

[4]. Hyun Tae Kim, et al. Structural Basis for Inhibitor-Induced Hydrogen Peroxide Production by Kynurenine 3-Monooxygenase. Cell Chem Biol. 2018 Apr 19;25(4):426-438.e4. [Content Brief]

[5]. Jingjing Gao, et al. Biochemistry and structural studies of kynurenine 3-monooxygenase reveal allosteric inhibition by Ro 61-8048. FASEB J. 2018 Apr;32(4):2036-2045. [Content Brief]

[6]. Jonathan P Hutchinson, et al. Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase. Nat Commun. 2017 Jun 12;8:15827. [Content Brief]

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