Paclitaxel electron crystallography

The first structural location of the taxane binding site [42] placed it in the interprotofilament space, thus supporting the biochemical results. However, this changed when the first high resolution 3D structure of the paclitaxel-tubulin complex was solved by electron-crystallography of a two-dimensional zinc-induced tubulin polymer [5]. The fitting of this structure into a three-dimensional reconstruction of microtubules from cryoelectron microscopy allowed a pseudo atomic resolution model of microtubules [43] in which the paclitaxel binding site was placed inside the lumen of the microtubules hidden from the outer solvent. 

Keywords Diffraction, Dynamics, Electron crystallography, Epothilone, Lauli-malide, Microtubules, Modeling, Paclitaxel, SAR, Taxol, Tubulin... 

The T-shape conformation was initially hypothesized as one of the possible paclitaxel conformations in chloroform, obtained by clusterization of a Monte Carlo conformational search [36], but no ultimate conclusion about the bioactive form could be obtained solely from the ligand-based studies. Eventually, this conformation was identified as the most promising one to fit into the electron crystallography (EC) density map of paxlitaxel-bound structure [79],... 

The First Electron Crystallography Structure of a,P-Tubulin/ Paclitaxel Complex... 

The binding of paclitaxel to microtubules has been studied extensively. The polymeric and noncrystalline nature of the tubulin-taxol complex prevents a direct approach by X-ray crystallography, but Lowe et al. (35) could determine the structure of tubulin at 3.5 A resolution by electron diffraction. Using this structure, various possible binding orientations of paclitaxel on tubulin have been proposed, but recent REDOR NMR... 

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