title: The role of the [2Fe-2s] cluster centers in xanthine oxidoreductase.
abstract: Xanthine oxidoreductases (XOR), xanthine dehydrogenase (XDH, EC1.1.1.204) and xanthine oxidase (XO, EC1.2.3.2), are the best-studied molybdenum-containing iron-sulfur flavoproteins. The mammalian enzymes exist originally as the dehydrogenase form (XDH) but can be converted to the oxidase form (XO) either reversibly by oxidation of sulfhydryl residues of the protein molecule or irreversibly by proteolysis. The active form of the enzyme is a homodimer of molecular mass 290 kDa. Each subunit contains one molybdopterin group, two non-identical [2Fe-2S] centers, and one flavin adenine dinucleotide (FAD) cofactor. This review focuses mainly on the role of the two iron-sulfur centers in catalysis, as recently elucidated by means of X-ray crystal structure and site-directed mutagenesis studies. The arrangements of cofactors indicate that the two iron-sulfur centers provide an electron transfer pathway from molybdenum to FAD. However, kinetic and thermodynamic studies suggest that these two iron-sulfur centers have roles not only in the pathway of electron flow, but also as an electron sink to provide electrons to the FAD center so that the reactivity of FAD with the electron acceptor substrate might be thermodynamically controlled by way of one-electron-reduced or fully reduced state.
authors.affiliation: Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan. nishino@nms.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Nishino
authors.forename: K
authors.initials: K
authors.lastname: Okamoto
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D016415:Sequence Alignment; D014968:Xanthine Dehydrogenase / Q000737:chemistry* / Q000378:metabolism; D014969:Xanthine Oxidase / Q000737:chemistry* / Q000378:metabolism; D014970:Xanthines / Q000737:chemistry / Q000378:metabolism*
chemical_list: D007506:Iron-Sulfur Proteins; D014970:Xanthines; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase