Interaction of the cyanobacterial thiazoline-containing lipid curacin A with bovine brain tubulin

Richard F. Ludueña, Veena Prasad, Mary C. Roach, Mohua Banerjee, Hye Dong Yoo, William H. Gerwick

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Curacin A is a thiazoline-containing lipid from the marine cyanobacterium Lyngbya majuscula. Despite being a potent inhibitor of microtubule assembly and of colchicine binding to tubulin, curacin A bears little or no structural resemblance to colchicine or to any other tubulin ligand. We investigated the interaction of curacin A with bovine brain tubulin using three different approaches. We first examined its effect on the intra-chain formation of a cross-link in β-tubulin by N,N'-ethylenebis(iodoacetamide). Formation of this cross-link, between cys239 and cys354, is blocked by colchicine and its A-ring analogues as well as by various other inhibitors of colchicine binding; C-ring analogues do not inhibit its formation. Curacin A strongly inhibited formation of this cross-link. Second, we examined the effect of curacin A on the time-dependent exposure of sulfhydryl groups on tubulin as measured by alkylation with iodo[14C]acetamide. Curacin A inhibited this very strongly, more so than either colchicine or podophyllotoxin. Last, we investigated the effect of curacin A on the time-dependent exposure of hydrophobic areas on the tubulin molecule. We found that curacin A had only a small effect on this process, comparable in magnitude to that of podophyllotoxin. Curacin A thus appears to have an unusual interaction with tubulin. Its binding site on tubulin is likely to overlap with that of the A-ring of colchicine.

Original languageEnglish (US)
Pages (from-to)223-229
Number of pages7
JournalDrug Development Research
Volume40
Issue number3
DOIs
StatePublished - Mar 1 1997

Keywords

  • Alkylation
  • Bis(8-anilinonaphthalene-1-sulfonate)
  • Curacin A
  • Microtubule
  • Tubulin

ASJC Scopus subject areas

  • Drug Discovery

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