1YFX

Crystal structure of 3-hydroxyanthranilate-3,4-dioxygenase from Ralstonia metallidurans complexed with 4-chloro-3-hydroxyanthranilic acid and NO

1YFX の概要

• エントリーDOI: 10.2210/pdb1yfx/pdb
• 関連するPDBエントリー: 1YFU 1YFW 1YFY
• 分子名称: 3-hydroxyanthranilate-3,4-dioxygenase, FE (III) ION, NITRIC OXIDE, ... (6 entities in total)
• 機能のキーワード: cupin, oxidoreductase
• 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: 20508.05

構造登録者

Zhang, Y.,Colabroy, K.L.,Begley, T.P.,Ealick, S.E. (登録日: 2005-01-04, 公開日: 2005-05-31, 最終更新日: 2024-02-14)

主引用文献

Zhang, Y.,Colabroy, K.L.,Begley, T.P.,Ealick, S.E.
Structural Studies on 3-Hydroxyanthranilate-3,4-dioxygenase: The Catalytic Mechanism of a Complex Oxidation Involved in NAD Biosynthesis.
Biochemistry, 44:7632-7643, 2005

PubMed Abstract: 3-Hydroxyanthranilate-3,4-dioxygenase (HAD) catalyzes the oxidative ring opening of 3-hydroxyanthranilate in the final enzymatic step of the biosynthetic pathway from tryptophan to quinolinate, the universal de novo precursor to the pyridine ring of nicotinamide adenine dinucleotide. The enzyme requires Fe2+ as a cofactor and is inactivated by 4-chloro-3-hydroxyanthranilate. HAD from Ralstonia metallidurans was crystallized, and the structure was determined at 1.9 A resolution. The structures of HAD complexed with the inhibitor 4-chloro-3-hydroxyanthranilic acid and either molecular oxygen or nitric oxide were determined at 2.0 A resolution, and the structure of HAD complexed with 3-hydroxyanthranilate was determined at 3.2 A resolution. HAD is a homodimer with a subunit topology that is characteristic of the cupin barrel fold. Each monomer contains two iron binding sites. The catalytic iron is buried deep inside the beta-barrel with His51, Glu57, and His95 serving as ligands. The other iron site forms an FeS4 center close to the solvent surface in which the sulfur atoms are provided by Cys125, Cys128, Cys162, and Cys165. The two iron sites are separated by 24 A. On the basis of the crystal structures of HAD, mutagenesis studies were carried out in order to elucidate the enzyme mechanism. In addition, a new mechanism for the enzyme inactivation by 4-chloro-3-hydroxyanthranilate is proposed.

PubMed: 15909978
DOI: 10.1021/bi047353l

実験手法

X-RAY DIFFRACTION (2 Å)