2D0U

Crystal structure of cyanide bound form of human indoleamine 2,3-dioxygenase

2D0U の概要

• エントリーDOI: 10.2210/pdb2d0u/pdb
• 関連するPDBエントリー: 2D0T
• 分子名称: Indoleamine 2,3-dioxygenase, CYANIDE ION, PROTOPORPHYRIN IX CONTAINING FE, ... (4 entities in total)
• 機能のキーワード: helix bundle, riken structural genomics/proteomics initiative, rsgi, structural genomics, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm, cytosol : P14902
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 93447.13

構造登録者

Sugimoto, H.,Oda, S.,Otsuki, T.,Hino, T.,Yoshida, T.,Shiro, Y.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (登録日: 2005-08-08, 公開日: 2006-01-31, 最終更新日: 2024-10-16)

主引用文献

Sugimoto, H.,Oda, S.,Otsuki, T.,Hino, T.,Yoshida, T.,Shiro, Y.
Crystal structure of human indoleamine 2,3-dioxygenase: catalytic mechanism of O2 incorporation by a heme-containing dioxygenase.
Proc.Natl.Acad.Sci.Usa, 103:2611-2616, 2006

PubMed Abstract: Human indoleamine 2,3-dioxygenase (IDO) catalyzes the cleavage of the pyrrol ring of L-Trp and incorporates both atoms of a molecule of oxygen (O2). Here we report on the x-ray crystal structure of human IDO, complexed with the ligand inhibitor 4-phenylimidazole and cyanide. The overall structure of IDO shows two alpha-helical domains with the heme between them. A264 of the flexible loop in the heme distal side is in close proximity to the iron. A mutant analysis shows that none of the polar amino acid residues in the distal heme pocket are essential for activity, suggesting that, unlike the heme-containing monooxygenases (i.e., peroxidase and cytochrome P450), no protein group of IDO is essential in dioxygen activation or proton abstraction. These characteristics of the IDO structure provide support for a reaction mechanism involving the abstraction of a proton from the substrate by iron-bound dioxygen. Inactive mutants (F226A, F227A, and R231A) retain substrate-binding affinity, and an electron density map reveals that 2-(N-cyclohexylamino)ethane sulfonic acid is bound to these residues, mimicking the substrate. These findings suggest that strict shape complementarities between the indole ring of the substrate and the protein side chains are required, not for binding, but, rather, to permit the interaction between the substrate and iron-bound dioxygen in the first step of the reaction. This study provides the structural basis for a heme-containing dioxygenase mechanism, a missing piece in our understanding of heme chemistry.

PubMed: 16477023
DOI: 10.1073/pnas.0508996103

実験手法

X-RAY DIFFRACTION (3.4 Å)