6XTI

NMR solution structure of class IV lasso peptide felipeptin A2 from Amycolatopsis sp. YIM10

6XTI の概要

• エントリーDOI: 10.2210/pdb6xti/pdb
• 関連するPDBエントリー: 6XTH
• NMR情報: BMRB: 34479
• 分子名称: Felipeptin A2 (1 entity in total)
• 機能のキーワード: lasso peptide, antibacterial, class iv, unknown function
• 由来する生物種: Amycolatopsis sp.
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1867.12

構造登録者

Madland, E.,Aachmann, F.L.,Guerrero-Garzon, J.F.,Zotchev, S.B.,Courtade, G. (登録日: 2020-01-16, 公開日: 2020-11-25, 最終更新日: 2024-11-06)

主引用文献

Guerrero-Garzon, J.F.,Madland, E.,Zehl, M.,Singh, M.,Rezaei, S.,Aachmann, F.L.,Courtade, G.,Urban, E.,Ruckert, C.,Busche, T.,Kalinowski, J.,Cao, Y.R.,Jiang, Y.,Jiang, C.L.,Selivanova, G.,Zotchev, S.B.
Class IV Lasso Peptides Synergistically Induce Proliferation of Cancer Cells and Sensitize Them to Doxorubicin.
Iscience, 23:101785-101785, 2020

PubMed Abstract: Heterologous expression of a biosynthesis gene cluster from sp. resulted in the discovery of two unique class IV lasso peptides, felipeptins A1 and A2. A mixture of felipeptins stimulated proliferation of cancer cells, while having no such effect on the normal cells. Detailed investigation revealed, that pre-treatment of cancer cells with a mixture of felipeptins resulted in downregulation of the tumor suppressor Rb, making the cancer cells to proliferate faster. Pre-treatment with felipeptins made cancer cells considerably more sensitive to the anticancer agent doxorubicin and re-sensitized doxorubicin-resistant cells to this drug. Structural characterization and binding experiments showed an interaction between felipeptins resulting in complex formation, which explains their synergistic effect. This discovery may open an alternative avenue in cancer treatment, helping to eliminate quiescent cells that often lead to cancer relapse.

PubMed: 33294793
DOI: 10.1016/j.isci.2020.101785

実験手法

SOLUTION NMR