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Gegenfurtner, Florian A
Crevenna, Alvaro H
Vollmar, Angelika M
MetadataShow full item record
AbstractActin is a protein of central importance for many cellular key processes. It is regulated by local interactions with a large number of actin binding proteins (ABPs). Various compounds are known to either increase or decrease the polymerization dynamics of actin. However, no actin binding compound has been developed for clinical applications yet because of selectivity issues. We provide a crystal structure of the natural product chivosazole A (ChivoA) bound to actin and show that-in addition to inhibiting nucleation, polymerization, and severing of F-actin filaments-it selectively modulates binding of ABPs to G-actin: Although unphysiological actin dimers are induced by ChivoA, interaction with gelsolin, profilin, cofilin, and thymosin-β4 is inhibited. Moreover, ChivoA causes transcriptional effects differing from latrunculin B, an actin binder with a different binding site. Our data show that ChivoA and related compounds could serve as scaffolds for the development of actin binding molecules selectively targeting specific actin functions.
CitationJ Nat Prod. 2019 Jul 26;82(7):1961-1970. doi: 10.1021/acs.jnatprod.9b00335. Epub 2019 Jul 1.
AffiliationHIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany.
PublisherAmerican Society for Chemistry
JournalJournal of natural products
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Direct Interaction of Chivosazole F with Actin Elicits Cell Responses Similar to Latrunculin A but Distinct from Chondramide.
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- Authors: Wang S, Crevenna AH, Ugur I, Marion A, Antes I, Kazmaier U, Hoyer M, Lamb DC, Gegenfurtner F, Kliesmete Z, Ziegenhain C, Enard W, Vollmar A, Zahler S
- Issue date: 2019 Jul 5