7QMU

Endothiapepsin in complex with compound TL00150 at room-temperature (temperature ramping up structure 4)

7QMU の概要

• エントリーDOI: 10.2210/pdb7qmu/pdb
• 関連するPDBエントリー: 7QLT 7QLU 7QLV 7QLW 7QLX 7QLY 7QLZ 7QM0 7QM1 7QM3 7QM4 7QM5 7QM6 7QM7 7QM8 7QM9 7QMA 7QMB 7QMC 7QMD 7QME 7QMF 7QMG 7QMH 7QMI 7QMJ 7QMK 7QML 7QMM 7QMN 7QMO 7QMP 7QMQ 7QMR 7QMS 7QMT 7QMV 7QMW 7QMX 7QMY 7QMZ 7QN0 7QN1 7QN2 7QN3 7QN4
• 分子名称: Endothiapepsin, [4-(trifluoromethyl)phenyl]methanamine, 1-METHOXY-2-[2-(2-METHOXY-ETHOXY]-ETHANE, ... (5 entities in total)
• 機能のキーワード: endopeptidase, hydrolase
• 由来する生物種: Cryphonectria parasitica (chestnut blight fungus)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44119.72

構造登録者

Huang, C.Y.,Aumonier, S.,Wang, M. (登録日: 2021-12-20, 公開日: 2022-08-17, 最終更新日: 2024-01-31)

主引用文献

Huang, C.Y.,Aumonier, S.,Engilberge, S.,Eris, D.,Smith, K.M.L.,Leonarski, F.,Wojdyla, J.A.,Beale, J.H.,Buntschu, D.,Pauluhn, A.,Sharpe, M.E.,Metz, A.,Olieric, V.,Wang, M.
Probing ligand binding of endothiapepsin by `temperature-resolved' macromolecular crystallography.
Acta Crystallogr D Struct Biol, 78:964-974, 2022

PubMed Abstract: Continuous developments in cryogenic X-ray crystallography have provided most of our knowledge of 3D protein structures, which has recently been further augmented by revolutionary advances in cryoEM. However, a single structural conformation identified at cryogenic temperatures may introduce a fictitious structure as a result of cryogenic cooling artefacts, limiting the overview of inherent protein physiological dynamics, which play a critical role in the biological functions of proteins. Here, a room-temperature X-ray crystallographic method using temperature as a trigger to record movie-like structural snapshots has been developed. The method has been used to show how TL00150, a 175.15 Da fragment, undergoes binding-mode changes in endothiapepsin. A surprising fragment-binding discrepancy was observed between the cryo-cooled and physiological temperature structures, and multiple binding poses and their interplay with DMSO were captured. The observations here open up new promising prospects for structure determination and interpretation at physiological temperatures with implications for structure-based drug discovery.

PubMed: 35916221
DOI: 10.1107/S205979832200612X

実験手法

X-RAY DIFFRACTION (1.79 Å)