Chivosazole A Modulates Protein-Protein Interactions of Actin.
J Nat Prod
; 82(7): 1961-1970, 2019 07 26.
Article
em En
| MEDLINE
| ID: mdl-31260301
ABSTRACT
Actin 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-ß4 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Actinas
/
Macrolídeos
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article