title: Rhizoxin binding to tubulin at the maytansine-binding site.
abstract: The binding of rhizoxin, a potent inhibitor of mitosis and in vitro microtubule assembly, to porcine brain tubulin was studied. Tubulin possesses one binding site for rhizoxin per molecule with a dissociation constant (Kd) of 1.7.10(-7) M. Ansamitocin P-3, a homologue of maytansine, was a competitive inhibitor of rhizoxin binding, with an inhibition constant of 1.3.10(-7) M. Vinblastine also inhibited rhizoxin binding, but was not fully competitive, and the inhibition constant was 2.9.10(-6) M. In contrast, both rhizoxin and ansamitocin P-3 were potent inhibitors of vinblastine binding. Rhizoxin inhibited tau-promoted tubulin assembly, but it, differing from vinblastine, did not induce tubulin aggregation into spirals, even at a concentration as high as 2.10(-5) M. In addition, rhizoxin strongly inhibited vinblastine-induced tau-dependent tubulin aggregation. Rhizoxin binding to tubulin was completely independent from colchicine binding. These effects resemble those of maytansine. The results suggested that rhizoxin binds to the maytansine-binding site and that the binding sites of rhizoxin and vinblastine are not the same.
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D003078:Colchicine / Q000494:pharmacology; D007700:Kinetics; D007783:Lactones / Q000378:metabolism; D018942:Macrolides; D008453:Maytansine / Q000031:analogs & derivatives / Q000378:metabolism*; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000648:ultrastructure; D010078:Oxazines / Q000378:metabolism*; D013552:Swine; D014404:Tubulin / Q000378:metabolism*; D014747:Vinblastine / Q000494:pharmacology; D016875:tau Proteins
chemical_list: D007783:Lactones; D018942:Macrolides; D008869:Microtubule-Associated Proteins; D010078:Oxazines; D014404:Tubulin; D016875:tau Proteins; D008453:Maytansine; D014747:Vinblastine; C015682:ansamitocins; C041443:rhizoxin; D003078:Colchicine