Taxol electron crystallography

Due to this lack of information, we and others invented the INPHARMA method that has been described above [75, 76], The prerequisites for INPHARMA are well fulfilled for EpoA and tubulin since the binding affinity is in the correct range, namely fast exchange. In addition, there is a 3D electron crystallography structure of the MT/taxol complex [11], Thus, INPHARMA could rely on this structure and derive from the interligand NOEs the orientation of EpoA in the binding pocket of tubulin. 

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

Based on analysis of electronic crystallography and NMR data for the bindings of Taxol and epothilone A to tubulin subunits, it was proposed that they did not share a common pharmacophore (similar binding mode and sites) as hypothesized for a long time, because they bind to their receptors uniquely and independently. Also, the T-shape conformation of Taxol binding to tubulin was supported from this study. 

The importance of the tubulin-polymerization activity of taxol has led to numerous studies of the taxol— tubulin interaction. The nature of the binding site of taxol on tubulin could not be determined by X-ray crystallography because the complex cannot be crystallized, but stabilized zinc sheets of microtubules can be prejjtared and the structure of these sheets has been determined by electron crystallography at a resolution of... 

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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