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- W2057202215 abstract "We compared the effects of dimeric marine toxins, bistheonellide A, and swinholide A, on actin polymerization. Bistheonellide A and swinholide A possess two identical side chains with similar structures to those of other marine toxins, mycalolide B, and aplyronine A. By monitoring changes in fluorescent intensity of pyrenyl-actin, bistheonellide A was found to inhibit polymerization of G-actin and to depolymerize F-actin in a concentration-dependent manner. The relationship between the concentration of bistheonellide A and its inhibitory activity on actin polymerization suggested that one molecule of bistheonellide A binds two molecules of G-actin. We demonstrated by SDS-PAGE that the complex of G-actin with bistheonellide A, swinholide A, or mycalolide B could not interact with myosin. No evidence was found that bistheonellide A severs F-actin at the concentrations examined (molar ratio to actin; 0. 025-2.5), while swinholide A showed severing activity, although it was weaker than that of mycalolide B. We also demonstrated that the depolymerizing effect of bistheonellide A or mycalolide B is irreversible. Bistheonellide A increased, while swinholide A decreased, the rate of nucleotide exchange in G-actin, suggesting that binding of these toxins induces different conformational changes in the actin molecule. These results suggest that bistheonellide A intervenes between two actin molecules, forms a tertiary complex with each of its side chains bound to G-actin, and inhibits polymerization by sequestering G-actin from incorporation into F-actin. A difference in structure at the end of the side chain between dimeric macrolides and mycalolide B may account for the weak severing activity of the former." @default.
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- W2057202215 date "1998-04-01" @default.
- W2057202215 modified "2023-10-06" @default.
- W2057202215 title "Actin-Depolymerizing Effect of Dimeric Macrolides, Bistheonellide A and Swinholide A" @default.
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- W2057202215 doi "https://doi.org/10.1093/oxfordjournals.jbchem.a021975" @default.
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