Actin-targeting natural products: structures, properties and mechanisms of action |
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Authors: | J S Allingham V A Klenchin I Rayment |
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Institution: | (1) Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, Wisconsin 53706, USA |
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Abstract: | Natural small-molecule inhibitors of actin cytoskeleton dynamics have long been recognized as valuable molecular probes for
dissecting complex mechanisms of cellular function. More recently, their potential use as chemotherapeutic drugs has become
a focus of scientific investigation. The primary focus of this review is the molecular mechanism by which different actin-targeting
natural products function, with an emphasis on structural considerations of toxins for which high-resolution structural information
of their interaction with actin is available. By comparing the molecular interactions made by different toxin families with
actin, the structural themes of those that alter filament dynamics in similar ways can be understood. This provides a framework
for novel synthetic-compound designs with tailored functional properties that could be applied in both research and clinical
settings.
Received 6 April 2006; received after revision 31 May 2006; accepted 19 June 2006 |
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Keywords: | Cytotoxic compound anti-cancer drugs actin filament dynamics sequestering capping severing filament stabilization |
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