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    J Am Chem Soc. 2007 Jan 17;129(2):361-70.

    Rotational-echo double-resonance NMR distance measurements for the tubulin-bound Paclitaxel conformation.

    Paik Y, Yang C, Metaferia B, Tang S, Bane S, Ravindra R, Shanker N, Alcaraz AA, Johnson SA, Schaefer J, O'Connor RD, Cegelski L, Snyder JP, Kingston DG.

    Department of Chemistry, M/C 0212, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA.

    The important anticancer drug Taxol (paclitaxel, PTX) owes its unique activity to its ability to bind to tubulin in a stoichiometric ratio and promote its assembly into microtubules. The conformation of the microtubule-bound drug has been the focus of numerous research efforts, since the inability of polymerized tubulin to form crystals precludes structure proof by X-ray crystallography. Likewise, although the alpha,beta-tubulin dimer structure has been solved by electron crystallography, the 3.7 A resolution is too low to permit direct determination of either ligand conformation or binding pose. In this article, we present experimental results from 2H{19F} REDOR NMR that provide direct confirmation that paclitaxel adopts a T-shaped conformation when it is bound to tubulin.

    PMID: 17212416 [PubMed - indexed for MEDLINE]

    PMCID: 2432525

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