Interaction of marine toxin dolastatin 10 with porcine brain tubulin: competitive inhibition of rhizoxin and phomopsin A binding.
Dolastatin 10, a cytostatic peptide containing several unique amino acid subunits, was isolated from the marine shell-less mollusk Dolabella auricularia. It inhibits microtubule assembly at concentrations below 5.0 microM (IC50, 3.0 microM) and causes formation of tubulin aggregates at higher (> 10 microM) concentrations in a somewhat different manner from that caused by vinblastine. Electron microscopical analysis showed irregular aggregates of microtubule proteins in the presence of 10 microM dolastatin 10. Dolastatin 10 inhibited the binding of both radiolabeled rhizoxin and phomopsin A to tubulin with inhibition constants (Ki) of 7 x 10(-8) M and 1 x 10(-7) M, respectively. The results suggest that at least one of the binding sites of dolastatin 10 on tubulin is the rhizoxin binding site.
Li
Y
Y
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Kobayashi
H
H
Hashimoto
Y
Y
Shirai
R
R
Hirata
A
A
Hayashi
K
K
Hamada
Y
Y
Shioiri
T
T
Iwasaki
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D047630:Depsipeptides; D007783:Lactones / Q000378:metabolism; D018942:Macrolides; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D008974:Mollusca; D009183:Mycotoxins / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D011108:Polymers; D013552:Swine; D014404:Tubulin / Q000737:chemistry* / Q000187:drug effects
D000970:Antineoplastic Agents; D047630:Depsipeptides; D007783:Lactones; D018942:Macrolides; D009183:Mycotoxins; D009842:Oligopeptides; D011108:Polymers; D014404:Tubulin; C035753:phomopsin; C041443:rhizoxin; C064570:dolastatin 10