7P0N

Crystal structure of L-Trp/Indoleamine 2,3-dioxygenagse 1 (hIDO1) complex with the JK-loop refined in the open conformation

7P0N の概要

• エントリーDOI: 10.2210/pdb7p0n/pdb
• 分子名称: Indoleamine 2,3-dioxygenase 1, PROTOPORPHYRIN IX CONTAINING FE, N'-Formylkynurenine, ... (9 entities in total)
• 機能のキーワード: l-trp metabolism, hemoprotein, dynamics loop, oxidoreductase
• 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: 187517.93

構造登録者

Mirgaux, M.,Wouters, J. (登録日: 2021-06-30, 公開日: 2021-12-29, 最終更新日: 2024-01-31)

主引用文献

Mirgaux, M.,Leherte, L.,Wouters, J.
Temporary Intermediates of L-Trp Along the Reaction Pathway of Human Indoleamine 2,3-Dioxygenase 1 and Identification of an Exo Site.
Int J Tryptophan Res, 14:11786469211052964-11786469211052964, 2021

PubMed Abstract: Protein dynamics governs most of the fundamental processes in the human body. Particularly, the dynamics of loops located near an active site can be involved in the positioning of the substrate and the reaction mechanism. The understanding of the functioning of dynamic loops is therefore a challenge, and often requires the use of a multi-disciplinary approach mixing, for example, crystallographic experiments and molecular dynamics simulations. In the present work, the dynamic behavior of the JK-loop of the human indoleamine 2,3-dioxygenase 1 hemoprotein, a target for immunotherapy, is investigated. To overcome the lack of knowledge on this dynamism, the study reported here is based on 3 crystal structures presenting different conformations of the loop, completed with molecular dynamics trajectories and MM-GBSA analyses, in order to trace the reaction pathway of the enzyme. In addition, the crystal structures identify an exo site in the small unit of the enzyme, that is populated redundantly by the substrate or the product of the reaction. The role of this newer reported exo site still needs to be investigated.

PubMed: 34949925
DOI: 10.1177/11786469211052964

実験手法

X-RAY DIFFRACTION (2.5 Å)