3nrz

Crystal Structure of Bovine Xanthine Oxidase in Complex with Hypoxanthine

spinqualitylabelsall models 3nrz, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3nrz is a 6 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FAD, FES, HPA, MOS, MTE Related: 3eub, 3etr, 3b9j Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [XDH_BOVIN] Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Xanthine oxidase is a molybdenum-containing enzyme catalyzing the hydroxylation of a sp(2)-hybridized carbon in a broad range of aromatic heterocycles and aldehydes. Crystal structures of the bovine enzyme in complex with the physiological substrate hypoxanthine at 1.8 A resolution and the chemotherapeutic agent 6-mercaptopurine at 2.6 A resolution have been determined, showing in each case two alternate orientations of substrate in the two active sites of the crystallographic asymmetric unit. One orientation is such that it is expected to yield hydroxylation at C-2 of substrate, yielding xanthine. The other suggests hydroxylation at C-8 to give 6,8-dihydroxypurine, a putative product not previously thought to be generated by the enzyme. Kinetic experiments demonstrate that >98% of hypoxanthine is hydroxylated at C-2 rather than C-8, indicating that the second crystallographically observed orientation is significantly less catalytically effective than the former. Theoretical calculations suggest that enzyme selectivity for the C-2 over C-8 of hypoxanthine is largely due to differences in the intrinsic reactivity of the two sites. For the orientation of hypoxanthine with C-2 proximal to the molybdenum center, the disposition of substrate in the active site is such that Arg(880) and Glu(802), previous shown to be catalytically important for the conversion of xanthine to uric acid, play similar roles in hydroxylation at C-2 as at C-8. Contrary to the literature, we find that 6,8-dihydroxypurine is effectively converted to uric acid by xanthine oxidase. Substrate orientation and catalytic specificity in the action of xanthine oxidase: the sequential hydroxylation of hypoxanthine to uric acid.,Cao H, Pauff JM, Hille R J Biol Chem. 2010 Sep 3;285(36):28044-53. Epub 2010 Jul 8. PMID:20615869 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Xanthine dehydrogenase

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