| Literature DB >> 15380187 |
Takeo Usui1, Sayaka Kazami, Naoshi Dohmae, Yoshikazu Mashimo, Hisae Kondo, Masashi Tsuda, Asako Goi Terasaki, Kazuyo Ohashi, Jun'ichi Kobayashi, Hiroyuki Osada.
Abstract
The actin-targeting toxins have not only proven to be invaluable tools in studies of actin cytoskeleton structure and function but they also served as a foundation for a new class of anticancer drugs. Here, we describe that amphidinolide H (AmpH) targets actin cytoskeleton. AmpH induced multinucleated cells by disrupting actin organization in the cells, and the hyperpolymerization of purified actin into filaments of apparently normal morphology in vitro. AmpH covalently binds on actin, and the AmpH binding site is determined as Tyr200 of actin subdomain 4 by mass spectrometry and halo assay using the yeast harboring site-directed mutagenized actins. Time-lapse analyses showed that AmpH stimulated the formation of small actin-patches, followed by F-actin rearrangement into aggregates via the retraction of actin fibers. These results indicate that AmpH is a novel actin inhibitor that covalently binds on actin.Entities:
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Year: 2004 PMID： 15380187 DOI： 10.1016/j.chembiol.2004.07.014
Source DB: PubMed Journal: Chem Biol ISSN： 1074-5521