3NVZ

Crystal Structure of Bovine Xanthine Oxidase in Complex with Indole-3-Aldehyde

3NVZ の概要

• エントリーDOI: 10.2210/pdb3nvz/pdb
• 関連するPDBエントリー: 3NVV 3NVW 3NVY
• 分子名称: Xanthine dehydrogenase/oxidase, FE2/S2 (INORGANIC) CLUSTER, FLAVIN-ADENINE DINUCLEOTIDE, ... (9 entities in total)
• 機能のキーワード: hydroxylase, homodimer, xanthine oxidase, indole-3-aldehyde, oxidoreductase
• 由来する生物種: Bos taurus (bovine,cow,domestic cattle,domestic cow); 詳細
• 細胞内の位置: Cytoplasm (By similarity): P80457 P80457 P80457
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 273664.77

構造登録者

Cao, H.,Hille, R. (登録日: 2010-07-08, 公開日: 2011-01-19, 最終更新日: 2024-02-21)

主引用文献

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

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: 24397336
DOI: 10.1021/bi401465u

実験手法

X-RAY DIFFRACTION (1.6 Å)