Maytansine inhibits nucleotide binding at the exchangeable site of tubulin.
The antineoplastic drug maytansine inhibits the binding of exogenously added radiolabeled GDP and GTP to tubulin (50% inhibition at 9-10 microM drug at 0 degrees). Vinblastine was 1/10-th as inhibitory. Neither maytansine nor vinblastine displaced GDP from tubulin, and both drugs virtually eliminated dissociation of radiolabeled GDP from the exchangeable site. Maytansine also inhibits binding of nucleotides to a vacant exchangeable site. Maytansine thus prevents nucleotide exit and entry at the exchangeable site because of a direct physical obstruction or a conformational change in the tubulin molecule.
D001665:Binding Sites; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D066298:In Vitro Techniques; D008453:Maytansine / Q000494:pharmacology*; D008870:Microtubules / Q000378:metabolism; D009711:Nucleotides / Q000378:metabolism*; D010078:Oxazines / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism*; D014747:Vinblastine / Q000494:pharmacology
D009711:Nucleotides; D010078:Oxazines; D014404:Tubulin; D008453:Maytansine; D006153:Guanosine Diphosphate; D014747:Vinblastine; D006160:Guanosine Triphosphate