8W2K

Crystal Structure of human Tryptophan 2,3-dioxygenase in complex with PAN3F inhibitor

これはPDB形式変換不可エントリーです。

8W2K の概要

• エントリーDOI: 10.2210/pdb8w2k/pdb
• 関連するPDBエントリー: 8VTQ 8VUG 8W1H 9AT2
• 分子名称: Tryptophan 2,3-dioxygenase, PROTOPORPHYRIN IX CONTAINING FE, alpha-methyl-L-tryptophan, ... (5 entities in total)
• 機能のキーワード: inhibitor, oxidoreductase, oxidoreductase-inhibitor complex, oxidoreductase/inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 185526.77

構造登録者

Geeraerts, Z.,Yeh, S.-R. (登録日: 2024-02-20, 公開日: 2024-08-21, 最終更新日: 2024-09-11)

主引用文献

Geeraerts, Z.,Ishigami, I.,Lewis-Ballester, A.,Pham, K.N.,Kozlova, A.,Mathieu, C.,Frederick, R.,Yeh, S.R.
Structural Insights into Protein-Inhibitor Interactions in Human Tryptophan Dioxygenase.
J.Med.Chem., 67:14543-14552, 2024

PubMed Abstract: Human tryptophan dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) are two important targets in cancer immunotherapy. Extensive research has led to a large number of potent IDO inhibitors; in addition, 52 structures of IDO in complex with inhibitors with a wide array of chemical scaffolds have been documented. In contrast, progress in the development of TDO inhibitors has been limited. Only four structures of TDO in complex with competitive inhibitors that compete with the substrate L-tryptophan for binding to the active site have been reported to date. Here we systematically evaluated the structures of TDO in complex with competitive inhibitors with three types of pharmacophores, imidazo-isoindole, indole-tetrazole, and indole-benzotriazole. The comparative assessment of the protein-inhibitor interactions sheds new light into the structure-based design of enzyme-selective inhibitors.

PubMed: 39106326
DOI: 10.1021/acs.jmedchem.4c01360

実験手法

X-RAY DIFFRACTION (2.45 Å)