3NVZ
Crystal Structure of Bovine Xanthine Oxidase in Complex with Indole-3-Aldehyde
Summary for 3NVZ
| Entry DOI | 10.2210/pdb3nvz/pdb |
| Related | 3NVV 3NVW 3NVY |
| Descriptor | Xanthine dehydrogenase/oxidase, FE2/S2 (INORGANIC) CLUSTER, FLAVIN-ADENINE DINUCLEOTIDE, ... (9 entities in total) |
| Functional Keywords | hydroxylase, homodimer, xanthine oxidase, indole-3-aldehyde, oxidoreductase |
| Biological source | Bos taurus (bovine,cow,domestic cattle,domestic cow) More |
| Cellular location | Cytoplasm (By similarity): P80457 P80457 P80457 |
| Total number of polymer chains | 6 |
| Total formula weight | 273664.77 |
| Authors | |
| Primary citation | Cao, H.,Hall, J.,Hille, R. Substrate orientation and specificity in xanthine oxidase: crystal structures of the enzyme in complex with indole-3-acetaldehyde and guanine. Biochemistry, 53:533-541, 2014 Cited by PubMed Abstract: Xanthine oxidase is a molybdenum-containing hydroxylase that catalyzes the hydroxylation of sp(2)-hybridized carbon centers in a variety of aromatic heterocycles as well as aldehydes. Crystal structures of the oxidase form of the bovine enzyme in complex with a poor substrate indole-3-acetaldehyde and the nonsubstrate guanine have been determined, both at a resolution of 1.6 Å. In each structure, a specific and unambiguous orientation of the substrate in the active site is observed in which the hydroxylatable site is oriented away from the active site molybdenum center. The orientation seen with indole-3-acetaldehyde has the substrate positioned with the indole ring rather than the exocyclic aldehyde nearest the molybdenum center, indicating that the substrate must rotate some 30° in the enzyme active site to permit hydroxylation of the aldehyde group (as observed experimentally), accounting for the reduced reactivity of the enzyme toward this substrate. The principal product of hydroxylation of indole-3-acetaldehyde by the bovine enzyme is confirmed to be indole-3-carboxylic acid based on its characteristic UV-vis spectrum, and the kinetics of enzyme reduction are reported. With guanine, the dominant orientation seen crystallographically has the C-8 position that might be hydroxylated pointed away from the active site molybdenum center, in a configuration resembling that seen previously with hypoxanthine (a substrate that is effectively hydroxylated at position 2). The ∼180° reorientation required to permit reaction is sterically prohibited, indicating that substrate (mis)orientation in the active site is a major factor precluding formation of the highly mutagenic 8-hydroxyguanine. PubMed: 24397336DOI: 10.1021/bi401465u PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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