Chemical Nature and Reaction Mechanisms of the Molybdenum Cofactor of Xanthine Oxidoreductase
| Autor: | Teruo Kusano, Ken Okamoto, Takeshi Nishino |
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| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular Xanthine Dehydrogenase molybdenum cofactor Stereochemistry Coenzymes Flavoprotein chemistry.chemical_element Hydroxylation Nitric Oxide Xanthine Article Substrate Specificity Electron Transport chemistry.chemical_compound Metalloproteins Drug Discovery Animals Humans Xanthine oxidase nitic oxide Hypoxanthine Pharmacology Oxipurinol biology complex flavoprotein Pteridines Hydrogen Bonding Uric Acid chemistry Xanthine dehydrogenase Molybdenum biology.protein Molybdenum cofactor Molybdenum Cofactors Oxidation-Reduction Protein Binding |
| Zdroj: | Current Pharmaceutical Design |
| ISSN: | 1381-6128 |
| DOI: | 10.2174/1381612811319140010 |
| Popis: | Xanthine oxidoreductase (XOR), a complex flavoprotein, catalyzes the metabolic reactions leading from hypoxanthine to xanthine and from xanthine to urate, and both reactions take place at the molybdenum cofactor. The enzyme is a target of drugs for therapy of gout or hyperuricemia. We review the chemical nature and reaction mechanisms of the molybdenum cofactor of XOR, focusing on molybdenum-dependent reactions of actual or potential medical importance, including nitric oxide (NO) synthesis. It is now generally accepted that XOR transfers the water-exchangeable -OH ligand of the molybdenum atom to the substrate. The hydroxyl group at OH-Mo(IV) can be replaced by urate, oxipurinol and FYX-051 derivatives and the structures of these complexes have been determined by x-ray crystallography under anaerobic conditions. Although formation of NO from nitrite or formation of xanthine from urate by XOR is chemically feasible, it is not yet clear whether these reactions have any physiological significance since the reactions are catalyzed at a slow rate even under anaerobic conditions. |
| Databáze: | OpenAIRE |
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