Maytansine inhibits nucleotide binding at the exchangeable site of tubulin

Biochem Biophys Res Commun. 1985 May 16;128(3):1239-46. doi: 10.1016/0006-291x(85)91073-3.

Abstract

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.

MeSH terms

  • Binding Sites
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • In Vitro Techniques
  • Maytansine / pharmacology*
  • Microtubules / metabolism
  • Nucleotides / metabolism*
  • Oxazines / pharmacology*
  • Tubulin / metabolism*
  • Vinblastine / pharmacology

Substances

  • Nucleotides
  • Oxazines
  • Tubulin
  • Maytansine
  • Guanosine Diphosphate
  • Vinblastine
  • Guanosine Triphosphate