Home
Resources
Publications
Actin Stabilizing Compounds Show Specific Biological Effects Due to Their Binding Mode

Actin Stabilizing Compounds Show Specific Biological Effects Due to Their Binding Mode

Shuaijun Wang, Alvaro H Crevenna, Ilke Ugur, Antoine Marion, Iris Antes, Uli Kazmaier, Maria Hoyer, Don C Lamb, Florian Gegenfurtner, Zane Kliesmete, Christoph Ziegenhain, Wolfgang Enard, Angelika Vollmar, etc.

Sci Rep. 2019 Jul 5;9(1):9731.

PMID: 31278311

Abstract:

Actin binding compounds are widely used tools in cell biology. We compare the biological and biochemical effects of miuraenamide A and jasplakinolide, a structurally related prototypic actin stabilizer. Though both compounds have similar effects on cytoskeletal morphology and proliferation, they affect migration and transcription in a distinctive manner, as shown by a transcriptome approach in endothelial cells. In vitro, miuraenamide A acts as an actin nucleating, F-actin polymerizing and stabilizing compound, just like described for jasplakinolide. However, in contrast to jasplakinolide, miuraenamide A competes with cofilin, but not gelsolin or Arp2/3 for binding to F-actin. We propose a binding mode of miuraenamide A, explaining both its similarities and its differences to jasplakinolide. Molecular dynamics simulations suggest that the bromophenol group of miurenamide A interacts with residues Tyr133, Tyr143, and Phe352 of actin. This shifts the D-loop of the neighboring actin, creating tighter packing of the monomers, and occluding the binding site of cofilin. Since relatively small changes in the molecular structure give rise to this selectivity, actin binding compounds surprisingly are promising scaffolds for creating actin binders with specific functionality instead of just "stabilizers".

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP102396247	Jasplakinolide		102396-24-7	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: