title: Crystal structures of urate bound form of xanthine oxidoreductase: substrate orientation and structure of the key reaction intermediate.
abstract: Two contradictory models have been proposed for the binding mode of the substrate xanthine to and its activation mechanism by xanthine oxidoreductase. In an effort to distinguish between the two models, we determined the crystal structures of the urate complexes of the demolybdo-form of the D428A mutant of rat xanthine oxidoreductase at 1.7 Å and of the reduced bovine milk enzyme at 2.1 Å, the latter representing a reaction intermediate. The results clearly indicate the catalytically relevant binding mode of the substrate xanthine.
authors.affiliation: Department of Biochemistry and Molecular Biology, Nippon Medical School, 1-1-5 Sendagi, Bunkyou-ku, Tokyo 113-8602, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Okamoto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Eger
authors.forename: Emil F
authors.initials: EF
authors.lastname: Pai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishino
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D002417:Cattle; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D051381:Rats; D014527:Uric Acid / Q000737:chemistry / Q000378:metabolism*; D014968:Xanthine Dehydrogenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D014527:Uric Acid; D014968:Xanthine Dehydrogenase