5O2A

FolD Q98H

5O2A の概要

• エントリーDOI: 10.2210/pdb5o2a/pdb
• 分子名称: Bifunctional protein FolD, ... (5 entities in total)
• 機能のキーワード: carolacton, fold, natural product, inhibitor, oxidoreductase
• 由来する生物種: Escherichia coli (strain K12); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 124718.20

構造登録者

Koehnke, J.,Sikandar, A. (登録日: 2017-05-19, 公開日: 2018-02-28, 最終更新日: 2024-01-17)

主引用文献

Fu, C.,Sikandar, A.,Donner, J.,Zaburannyi, N.,Herrmann, J.,Reck, M.,Wagner-Dobler, I.,Koehnke, J.,Muller, R.
The natural product carolacton inhibits folate-dependent C1 metabolism by targeting FolD/MTHFD.
Nat Commun, 8:1529-1529, 2017

PubMed Abstract: The natural product carolacton is a macrolide keto-carboxylic acid produced by the myxobacterium Sorangium cellulosum, and was originally described as an antibacterial compound. Here we show that carolacton targets FolD, a key enzyme from the folate-dependent C1 metabolism. We characterize the interaction between bacterial FolD and carolacton biophysically, structurally and biochemically. Carolacton binds FolD with nanomolar affinity, and the crystal structure of the FolD-carolacton complex reveals the mode of binding. We show that the human FolD orthologs, MTHFD1 and MTHFD2, are also inhibited in the low nM range, and that micromolar concentrations of carolacton inhibit the growth of cancer cell lines. As mitochondrial MTHFD2 is known to be upregulated in cancer cells, it may be possible to use carolacton as an inhibitor tool compound to assess MTHFD2 as an anti-cancer target.

PubMed: 29142318
DOI: 10.1038/s41467-017-01671-5

実験手法

X-RAY DIFFRACTION (1.9 Å)