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Nucleosides Nucleotides Nucleic Acids. 2008 Jun;27(6):888-93. doi: 10.1080/15257770802146577.

Mechanism of inhibition of xanthine oxidoreductase by allopurinol: crystal structure of reduced bovine milk xanthine oxidoreductase bound with oxipurinol.

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1
Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan.

Abstract

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 A 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 glutamate 802, arginine 880, and glutamate 1261, 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.

PMID:
18600558
DOI:
10.1080/15257770802146577
[Indexed for MEDLINE]

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