6QRI

Structure of rabbit G-actin in complex with chivosazole A

6QRI の概要

• エントリーDOI: 10.2210/pdb6qri/pdb
• 分子名称: Actin, alpha skeletal muscle, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: cytoskeleton, macrolide, myxobacteria, cytosolic protein
• 由来する生物種: Oryctolagus cuniculus (Rabbit)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 87015.09

構造登録者

Schneider, S.,Wang, S.,Zahler, S. (登録日: 2019-02-19, 公開日: 2019-07-03, 最終更新日: 2024-01-24)

主引用文献

Wang, S.,Gegenfurtner, F.A.,Crevenna, A.H.,Ziegenhain, C.,Kliesmete, Z.,Enard, W.,Muller, R.,Vollmar, A.M.,Schneider, S.,Zahler, S.
Chivosazole A Modulates Protein-Protein Interactions of Actin.
J.Nat.Prod., 82:1961-1970, 2019

PubMed 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-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.

PubMed: 31260301
DOI: 10.1021/acs.jnatprod.9b00335

実験手法

X-RAY DIFFRACTION (2.4 Å)