6XTH

NMR solution structure of class IV lasso peptide felipeptin A1 from Amycolatopsis sp. YIM10

Summary for 6XTH

• Entry DOI: 10.2210/pdb6xth/pdb
• Related: 6XTI
• NMR Information: BMRB: 34478
• Descriptor: Felipeptin A1 (1 entity in total)
• Functional Keywords: lasso peptide, antibacterial, class iv, unknown function
• Biological source: Amycolatopsis sp.
• Total number of polymer chains: 1
• Total formula weight: 2040.33

Authors

Madland, E.,Guerrero-Garzon, J.F.,Zotchev, S.B.,Aachmann, F.L.,Courtade, G. (deposition date: 2020-01-16, release date: 2020-11-25, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

SOLUTION NMR