Taxol allosterically alters the dynamics of the tubulin dimer and increases the flexibility of microtubules.

ABSTRACT: Taxol is a commonly used antitumor agent that hyperstabilizes microtubules and prevents cell division. The interaction of Taxol with tubulin and the microtubule has been studied through a wide array of experimental techniques; however, the exact molecular mechanism by which Taxol stabilizes microtubules has remained elusive. In this study, through the use of large-scale molecular simulations, we show that Taxol affects the interactions between the M and H1-S2 loops of adjacent tubulin dimers leading to more stable interprotofilament interactions. More importantly, we demonstrate that Taxol binding leads to a significant increase in the dynamics and flexibility of the portion of beta-tubulin that surrounds the bound nucleotide and makes contact with the alpha-monomer of the next dimer in th

SUBMITTER: Mitra A 

PROVIDER: S-EPMC2547448 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature