期刊
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS
卷 27, 期 6-7, 页码 888-893出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15257770802146577
关键词
xanthine oxidase; xanthine dehydrogenase; xanthine oxidoreductase; gout; hyperuricemia; allopurinol; febuxostat
Inhibitors of xanthine oxidoreductase block conversion of xanthine to uric acid and are therefore potentially useful for treatment of hyperuricemia or gout. We determined the crystal structure of reduced bovine milk xanthine oxidoreductase complexed with oxipurinol at 2.0 resolution. Clear electron density was observed between the N2 nitrogen of oxipurinol and the molybdenum atom of the molybdopterin cofactor, indicating that oxipurinol coordinated directly to molybdenum. Oxipurinol forms hydrogen bonds with glutamate802, arginine880, and glutamate1261, which have previously been shown to be essential for the enzyme reaction. We discuss possible differences in the hypouricemic effect of inhibitors, including allopurinol and newly developed inhibitors, based on their mode of binding in the crystal structures.
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