title: Kynurenine-3-monooxygenase: a review of structure, mechanism, and inhibitors.
abstract: Kynurenine monooxygenase (KMO) is an enzyme of the kynurenine (Kyn) pathway (KP), which is the major catabolic route of tryptophan. Kyn represents a branch point of the KP, being converted into the neurotoxin 3-hydroxykynurenine via KMO, neuroprotectant kynurenic acid, and anthranilic acid. As a result of this branch point, KMO is an attractive drug target for several neurodegenerative and/or neuroinflammatory diseases, especially Huntington's (HD), Alzheimer's (AD), and Parkinson's (PD) diseases. Although a neurological target, administration of KMO inhibitors in the periphery has demonstrated promising pharmacological results. In light of a recent crystal structure release and reports of preclinical candidates, here we provide a concise yet comprehensive update on the current state of research into the enzymology of KMO and related drug discovery efforts, highlighting areas where further work is required.
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW 2109, Australia.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Smith
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW 2109, Australia. Electronic address: joanne.jamie@mq.edu.au.
authors.forename: Joanne F
authors.initials: JF
authors.lastname: Jamie
authors.affiliation: Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia.
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D050601:Kynurenine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D019636:Neurodegenerative Diseases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology
chemical_list: D050601:Kynurenine 3-Monooxygenase