Novel actin depolymerizing macrolide aplyronine A.
Aplyronine A is a macrolide isolated from Aplysia kurodai. By monitoring fluorescent intensity of pyrenyl-actin, it was found that aplyronine A inhibited both the velocity and the degree of actin polymerization. Aplyronine A also quickly depolymerized F-actin. The kinetics of depolymerization suggest that aplyronine A severs F-actin. The relationship between the concentration of total actin and F-actin at different concentrations of aplyronine A suggests that aplyronine A forms a 1:1 complex with G-actin. From these results, it is concluded that aplyronine A inhibits actin polymerization and depolymerizes F-actin by nibbling. Comparison of the chemical structure of aplyronine A and another actin-depolymerizing macrolide, mycalolide B, suggests that the side-chain but not the macrolide ring of aplyronine A may account for its actin binding and severing activity.
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University of Tokyo.
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S
Saito
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Watabe
H
H
Ozaki
H
H
Kigoshi
K
K
Yamada
N
N
Fusetani
H
H
Karaki
D000199:Actins / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001048:Aplysia; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007700:Kinetics; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D018942:Macrolides; D008387:Marine Toxins; D018482:Muscle, Skeletal / Q000378:metabolism; D009218:Myosins / Q000037:antagonists & inhibitors; D010080:Oxazoles / Q000737:chemistry / Q000494:pharmacology; D010590:Phalloidine / Q000494:pharmacology; D011817:Rabbits; D012694:Serine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D014335:Tropomyosin / Q000378:metabolism
D000199:Actins; D004791:Enzyme Inhibitors; D007783:Lactones; D018942:Macrolides; D008387:Marine Toxins; D010080:Oxazoles; D014335:Tropomyosin; C080978:mycalolide B; C104057:aplyronine A; D010590:Phalloidine; D012694:Serine; D009218:Myosins