The Binding Mode of Epothilone A on α,ß-Tubulin by Electron Crystallography

• DOI: 10.1126/science.1099190
• Publication Date: 2004-08-05T20:18:15Z
• Authors: James H. Nettles; Huilin Li; Ben Cornett; Joseph M. Krahn; James P. Snyder; Kenneth H. Downing
• Keywords: Epothilones

The structure of epothilone A, bound to alpha,beta-tubulin in zinc-stabilized sheets, was determined by a combination electron crystallography at 2.89 angstrom resolution and nuclear magnetic resonance-based conformational analysis. complex explains both the broad-based structure-activity relationship known mutational resistance profile. Comparison with Taxol shows that longstanding expectation common pharmacophore is not met, because each ligand exploits tubulin-binding pocket unique independent manner.