Sharing microtubule-stabilizing

The initial observation that paclitaxel (PTX) stabilized the zinc sheet form of tubulin at nanomolar concentrations suggested that there was a high affinity binding site in these polymers like that found on microtubules. However, it was not a priori certain that the binding site on sheets would have the same geometry even if it were in the same location. The derivation of high resolution models of both polymers that show the same dimer structure supports the conclusion that, indeed, they share the same binding site. 

The antimitotic mechanism of taxol differs from the antimicrotubule agents such as colchicine and the vinca alkaloids discussed earlier. Rather than causing disassembly of the microtubules, taxol actually enhances tubulin polymerization. This upsets the normal dynamic equilibrium between soluble tubules, which are dimers, and the microtubule polymers. The stabilization of the latter inhibits mitosis in the latter part of Phase G2 and M. Although sharing much of the toxicology of many of the anticancer drugs, taxol promises to be an important addition to the cancer armamentarium. 

Microtubules are essential organelles involved in cihary function. Tectins, which share some structural homology with intermediate filament proteins but are uniquely different, could act to stabilize the pf-ribbon located in the doublet microtubule and thus the microtubule itself (Linck 1995). 

Paclitaxel and other taxanes accelerate tubulin polymerization by stabilizing already assembled microtubules and thus preventing the depolymerization of microtubules. The fungal metabolites epothilone A and B share some of the binding characteristics of taxanes (40,41). 

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