4HSJ

1.88 angstrom x-ray crystal structure of piconlinic-bound 3-hydroxyanthranilate-3,4-dioxygenase

4HSJ の概要

• エントリーDOI: 10.2210/pdb4hsj/pdb
• 関連するPDBエントリー: 4HSK 4HSL 4HSM
• 分子名称: 3-hydroxyanthranilate 3,4-dioxygenase, FE (II) ION, PYRIDINE-2-CARBOXYLIC ACID, ... (4 entities in total)
• 機能のキーワード: bi-cupin, dioxygenase, oxidoreductase, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 由来する生物種: Cupriavidus metallidurans
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20291.43

構造登録者

Liu, F.,Chen, L.,Davis, C.I.,Liu, A. (登録日: 2012-10-30, 公開日: 2015-05-06, 最終更新日: 2023-09-20)

主引用文献

Liu, F.,Geng, J.,Gumpper, R.H.,Barman, A.,Davis, I.,Ozarowski, A.,Hamelberg, D.,Liu, A.
An Iron Reservoir to the Catalytic Metal: THE RUBREDOXIN IRON IN AN EXTRADIOL DIOXYGENASE.
J.Biol.Chem., 290:15621-15634, 2015

PubMed Abstract: The rubredoxin motif is present in over 74,000 protein sequences and 2,000 structures, but few have known functions. A secondary, non-catalytic, rubredoxin-like iron site is conserved in 3-hydroxyanthranilate 3,4-dioxygenase (HAO), from single cellular sources but not multicellular sources. Through the population of the two metal binding sites with various metals in bacterial HAO, the structural and functional relationship of the rubredoxin-like site was investigated using kinetic, spectroscopic, crystallographic, and computational approaches. It is shown that the first metal presented preferentially binds to the catalytic site rather than the rubredoxin-like site, which selectively binds iron when the catalytic site is occupied. Furthermore, an iron ion bound to the rubredoxin-like site is readily delivered to an empty catalytic site of metal-free HAO via an intermolecular transfer mechanism. Through the use of metal analysis and catalytic activity measurements, we show that a downstream metabolic intermediate can selectively remove the catalytic iron. As the prokaryotic HAO is often crucial for cell survival, there is a need for ensuring its activity. These results suggest that the rubredoxin-like site is a possible auxiliary iron source to the catalytic center when it is lost during catalysis in a pathway with metabolic intermediates of metal-chelating properties. A spare tire concept is proposed based on this biochemical study, and this concept opens up a potentially new functional paradigm for iron-sulfur centers in iron-dependent enzymes as transient iron binding and shuttling sites to ensure full metal loading of the catalytic site.

PubMed: 25918158
DOI: 10.1074/jbc.M115.650259

実験手法

X-RAY DIFFRACTION (1.883 Å)