Actin-targeting natural products: structures, properties and mechanisms of action.
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.
Allingham
J S
JS
Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, Wisconsin 53706, USA.
Klenchin
V A
VA
Rayment
I
I
D000199:Actins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001688:Biological Products; D002465:Cell Movement / Q000187:drug effects*; D003599:Cytoskeleton / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008387:Marine Toxins; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction
D000199:Actins; D001688:Biological Products; D008387:Marine Toxins; D008840:Microfilament Proteins; D019204:GTP-Binding Proteins