Microtubule-Destabilizing Agents: Structural and Mechanistic Insights from the Interaction of Colchicine and Vinblastine with Tubulin B. Gigant, A. Cormier, A. Dorléans, R.B.G. Ravelli, and M. Knossow B. Gigant ( ü *), A. Cormier, A. Dorléans, and M. Knossow ( ü *) Laboratoire d’Enzymologie et Biochimie Structurales (LEBS), CNRS, Bat. 34, 1 avenue de la Terrasse, 91198 Gif-sur-Yvette, France e-mail: gigant@lebs.cnrs-gif.fr, knossow@lebs.cnrs-gif.fr R.B.G. Ravelli European Molecular Biology Laboratory (EMBL), Grenoble Outstation, 6 rue Jules Horowitz, BP 181, 38042, Grenoble, France Present address: Leiden University Medical Center (LUMC) 2333 ZC Einthovenweg 20, Leiden, The Netherlands A. Dorléans Present Address: Laboratoire d’Enzymologie et Biochimie Structurales (LEBS), CNRS, Bat. 34, 1 avenue de la Terrasse, 91198 Gif-sur-Yvette, France Institut de Biologie Physico-Chimique (IBPC), CNRS, 13, rue Pierre et Marie Curie - 75005 Paris, France Abstract Microtubules (MTs) are dynamic structures of the eukaryotic cytoskeleton that, during cell division, form the mitotic spindle. Perturbing them leads to mitotic arrest and ultimately to cell death. Consistently, MTs and their building block, αβ tubulin, are one of the best characterized targets in anti-cancer chemotherapy. Drugs that interfere with MTs either stabilize or destabilize them. The latter class is the sub- ject of this review. These ligands bind to the colchicine site or to the vinca domain, two distinct sites located at a distance from each other on tubulin. Nevertheless the effects of both classes of ligands share a common theme, they prevent the formation of MT specific contacts, therefore triggering their disassembly. Keywords Cytoskeleton, Microtubule dynamics, Mitosis, Structure Vinca domain Top Curr Chem (2009) 286: 259–278 DOI: 10.1007/128_2008_11 © Springer-Verlag Berlin Heidelberg 2009 Published online: 16 October 2008