7S8Z

Room-temperature apo Human Hsp90a-NTD

7S8Z の概要

• エントリーDOI: 10.2210/pdb7s8z/pdb
• 分子名称: Heat shock protein HSP 90-alpha (2 entities in total)
• 機能のキーワード: chaperone protein, signal transduction, heat shock, chaperone, hydrolase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26739.92

構造登録者

Stachowski, T.R.,Vanarotti, M.,Lopez, K.,Fischer, M. (登録日: 2021-09-20, 公開日: 2022-08-03, 最終更新日: 2023-10-18)

主引用文献

Stachowski, T.R.,Vanarotti, M.,Seetharaman, J.,Lopez, K.,Fischer, M.
Water Networks Repopulate Protein-Ligand Interfaces with Temperature.
Angew.Chem.Int.Ed.Engl., 61:e202112919-e202112919, 2022

PubMed Abstract: High-resolution crystal structures highlight the importance of water networks in protein-ligand interactions. However, as these are typically determined at cryogenic temperature, resulting insights may be structurally precise but not biologically accurate. By collecting 10 matched room-temperature and cryogenic datasets of the biomedical target Hsp90α, we identified changes in water networks that impact protein conformations at the ligand binding interface. Water repositioning with temperature repopulates protein ensembles and ligand interactions. We introduce Flipper conformational barcodes to identify temperature-sensitive regions in electron density maps. This revealed that temperature-responsive states coincide with ligand-responsive regions and capture unique binding signatures that disappear upon cryo-cooling. Our results have implications for discovering Hsp90 selective ligands, and, more generally, for the utility of hidden protein and water conformations in drug discovery.

PubMed: 35648650
DOI: 10.1002/anie.202112919

実験手法

X-RAY DIFFRACTION (1.64 Å)