8F2K

Structure of yeast F1-ATPase determined with 100 micromolar cruentaren A

8F2K の概要

• エントリーDOI: 10.2210/pdb8f2k/pdb
• EMDBエントリー: 28818
• 分子名称: ATP synthase subunit alpha, ATP synthase subunit beta, ATP synthase subunit gamma, ... (6 entities in total)
• 機能のキーワード: f1-atpase, atp synthase, cruentaren a, drug development, hydrolase
• 由来する生物種: Saccharomyces cerevisiae (baker's yeast); 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 342504.27

構造登録者

Guo, H.,Rubinstein, J.L. (登録日: 2022-11-08, 公開日: 2023-04-05, 最終更新日: 2024-04-24)

主引用文献

Dou, X.,Guo, H.,D'Amico, T.,Abdallah, L.,Subramanian, C.,Patel, B.A.,Cohen, M.,Rubinstein, J.L.,Blagg, B.S.J.
CryoEM Structure with ATP Synthase Enables Late-Stage Diversification of Cruentaren A.
Chemistry, 29:e202300262-e202300262, 2023

PubMed Abstract: Cruentaren A is a natural product that exhibits potent antiproliferative activity against various cancer cell lines, yet its binding site within ATP synthase remained unknown, thus limiting the development of improved analogues as anticancer agents. Herein, we report the cryogenic electron microscopy (cryoEM) structure of cruentaren A bound to ATP synthase, which allowed the design of new inhibitors through semisynthetic modification. Examples of cruentaren A derivatives include a trans-alkene isomer, which was found to exhibit similar activity to cruentaren A against three cancer cell lines as well as several other analogues that retained potent inhibitory activity. Together, these studies provide a foundation for the generation of cruentaren A derivatives as potential therapeutics for the treatment of cancer.

PubMed: 36867738
DOI: 10.1002/chem.202300262

実験手法

ELECTRON MICROSCOPY (2.9 Å)