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16 April 2024

» pubmed » pmid15297674

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The binding mode of epothilone A on alpha,beta-tubulin by electron crystallography
James H Nettles ; Huilin Li ; Ben Cornett ; Joseph M Krahn ; James P Snyder ; Kenneth H Downing ;
Date:	6 Aug 2004
Journal:	Science, 305 (5685), 866-9
Abstract:	The structure of epothilone A, bound to alpha,beta-tubulin in zinc-stabilized sheets, was determined by a combination of electron crystallography at 2.89 angstrom resolution and nuclear magnetic resonance-based conformational analysis. The complex explains both the broad-based epothilone structure-activity relationship and the known mutational resistance profile. Comparison with Taxol shows that the longstanding expectation of a common pharmacophore is not met, because each ligand exploits the tubulin-binding pocket in a unique and independent manner.
Source:	PubMed, pmid15297674 doi: 10.1126/science.1099190
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