Binding of colchiceine to tubulin. Mechanisms of ligand association with tubulin.
Colchiceine, a closely related structural analog of colchicine possessing a C-ring tropolone, has been shown to be a potent inhibitor of microtubule assembly in vitro (I50 = 20 microM). The mechanism of inhibition is mediated through binding to tubulin (KA = 1.2 +/- 0.7 x 10(4) M-1), although potentially not through the colchicine receptor site. Supporting the hypothesis of an alternate receptor are the observation of colchiceine binding to the isolated colchicine-tubulin complex (KA = 2.2 +/- 1.0 x 10(4) M-1), the poor correlation between the competitive inhibition of colchicine binding (KI = 125 microM) and the inhibition of microtubule assembly, and different structure-activity relationships for colchiceine analogs as compared to the colchicine series.
Hastie
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SB
Department of Chemistry, University of Virginia, Charlottesville 22901.
Macdonald
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TL
D001667:Binding, Competitive; D001704:Biopolymers; D003078:Colchicine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D011485:Protein Binding; D014404:Tubulin / Q000378:metabolism*
D001704:Biopolymers; D014404:Tubulin; C012852:colchiceine; D003078:Colchicine