Effect of phomopsin a on the alkylation of tubulin

Richard F. Ludueña, Mary Carmen Roach, Veena Prasad, Ernest Lacey

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Phomopsin A, a macrocyclic heptapeptide isolated from the fungus Phomopsis leptostromiformis, is a potent inhibitor of microtubule assembly and of vinblastine binding to tubulin. Like vinblastine, phomopsin A stabilizes colchicine binding to tubulin. Because phomopsin A is structurally very different from either vinblastine or maytansine, it was of interest to compare its effects on tubulin sulfhydryls to those of the other two drugs. Our results indicate that the effects of phomopsin A combine those of maytansine and vinblastine. Like maytansine, phomopsin A completely inhibited formation of a covalent cross-link between cysteines 12 and 201 or 211, induced by N,N'-ethylenebis(iodoacetamide); like vinblastine, phomopsin A strongly inhibited alkylation of tubulin by iodo[14C]acetamide. Our results are consistent with the hypothesis that phomopsin A binds to regions on tubulin overlapping those to which vinblastine and maytansine bind. We have shown previously that phomopsin A is a potent stabilizer of the tubulin molecule. We now find that when both phomopsin A and colchicine are bound to tubulin, the rate of decay of colchicine binding becomes insignificant.

Original languageEnglish (US)
Pages (from-to)1603-1608
Number of pages6
JournalBiochemical Pharmacology
Volume39
Issue number10
DOIs
StatePublished - May 15 1990

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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