4N9M

Joint neutron/x-ray structure of urate oxidase in complex with 8-hydroxyxanthine

4N9M の概要

• エントリーDOI: 10.2210/pdb4n9m/pdb
• 関連するPDBエントリー: 3L9G 4N3M 4N9S 4N9V
• 分子名称: Uricase, 8-hydroxy-3,9-dihydro-1H-purine-2,6-dione, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: urate oxidase, uricase oxidoreductase, oxidoreductase
• 由来する生物種: Aspergillus flavus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34410.14

構造登録者

Oksanen, E.,Blakeley, M.P.,Budayova-Spano, M. (登録日: 2013-10-21, 公開日: 2014-02-05, 最終更新日: 2024-11-20)

主引用文献

Oksanen, E.,Blakeley, M.P.,El-Hajji, M.,Ryde, U.,Budayova-Spano, M.
The neutron structure of urate oxidase resolves a long-standing mechanistic conundrum and reveals unexpected changes in protonation.
Plos One, 9:e86651-e86651, 2014

PubMed Abstract: Urate oxidase transforms uric acid to 5-hydroxyisourate without the help of cofactors, but the catalytic mechanism has remained enigmatic, as the protonation state of the substrate could not be reliably deduced. We have determined the neutron structure of urate oxidase, providing unique information on the proton positions. A neutron crystal structure inhibited by a chloride anion at 2.3 Å resolution shows that the substrate is in fact 8-hydroxyxanthine, the enol tautomer of urate. We have also determined the neutron structure of the complex with the inhibitor 8-azaxanthine at 1.9 Å resolution, showing the protonation states of the K10-T57-H256 catalytic triad. Together with X-ray data and quantum chemical calculations, these structures allow us to identify the site of the initial substrate protonation and elucidate why the enzyme is inhibited by a chloride anion.

PubMed: 24466188
DOI: 10.1371/journal.pone.0086651

実験手法

NEUTRON DIFFRACTION (2.298 Å)
X-RAY DIFFRACTION (2.023 Å)