The interaction of phomopsin A with bovine brain tubulin

Arch Biochem Biophys. 1989 Jul;272(1):32-8. doi: 10.1016/0003-9861(89)90191-4.

Abstract

Phomopsin A is an anti-mitotic compound from the fungus Phomopsis leptostroniformis which is a potent inhibitor of microtubule assembly in vitro; like maytansine, it is known to compete with vinblastine for binding to tubulin (E. Lacey, J. A. Edgar, and C. C. J. Culvenor (1987) Biochem. Pharmacol. 36, 2133-2138). A major difference between the effects of maytansine and vinblastine is that vinblastine is a potent inhibitor of tubulin decay, whereas maytansine has little or no effect on decay. Since phomopsin A is structurally distinct from either maytansine or vinblastine, tubulin decay may be measured by either the time-dependent loss of the ability to bind to [3H]colchicine or the time-dependent increase in the binding of bis(8-anilinonaphthalene 1-sulfonate) (BisANS) to tubulin. By either method, phomopsin A was found to be a much stronger inhibitor of tubulin decay than is vinblastine or any other drug yet tested, and in fact, when decay is measured by the increase of BisANS binding, phomopsin A appears to stop the process entirely. This may prove to be useful in the determination of the higher-order structure of the tubulin molecule.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anilino Naphthalenesulfonates / metabolism
  • Animals
  • Brain Chemistry*
  • Cattle
  • Colchicine / metabolism
  • Fluorescent Dyes
  • Kinetics
  • Maytansine / pharmacology
  • Molecular Structure
  • Mycotoxins / pharmacology*
  • Spectrometry, Fluorescence
  • Tubulin / metabolism*
  • Vinblastine / pharmacology

Substances

  • Anilino Naphthalenesulfonates
  • Fluorescent Dyes
  • Mycotoxins
  • Tubulin
  • Maytansine
  • Vinblastine
  • 5,5'-bis(8-(phenylamino)-1-naphthalenesulfonate)
  • phomopsin
  • Colchicine