title: Mechanistic insights into xanthine oxidoreductase from development studies of candidate drugs to treat hyperuricemia and gout.
abstract: Xanthine oxidoreductase (XOR), which is widely distributed from humans to bacteria, has a key role in purine catabolism, catalyzing two steps of sequential hydroxylation from hypoxanthine to xanthine and from xanthine to urate at its molybdenum cofactor (Moco). Human XOR is considered to be a target of drugs not only for therapy of hyperuricemia and gout, but also potentially for a wide variety of other diseases. In this review, we focus on studies of XOR inhibitors and their implications for understanding the chemical nature and reaction mechanism of the Moco active site of XOR. We also discuss further experimental or clinical studies that would be helpful to clarify remaining issues.
authors.affiliation: Department of Biochemistry and Molecular Biology, Nippon Medical School, 1-1-5 Sendagi, Bunkyou-ku, Tokyo, 113-8602, Japan, nishino@nms.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishino
authors.forename: Ken
authors.initials: K
authors.lastname: Okamoto
mesh_terms: D020134:Catalytic Domain; D003067:Coenzymes / Q000737:chemistry* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006073:Gout / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D033461:Hyperuricemia / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D008667:Metalloproteins / Q000737:chemistry* / Q000378:metabolism; D000090006:Molybdenum Cofactors; D011621:Pteridines / Q000737:chemistry* / Q000378:metabolism; D019820:Xanthine / Q000737:chemistry; D014968:Xanthine Dehydrogenase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D003067:Coenzymes; D004791:Enzyme Inhibitors; D008667:Metalloproteins; D000090006:Molybdenum Cofactors; D011621:Pteridines; D019820:Xanthine; D014968:Xanthine Dehydrogenase; C022261:molybdopterin