A ribbon diagram based on the 3.7 angstrom resolution model of tubulin developed at Berkeley Lab, shows a dimer consisting of two almost identical monomers. In addition to a nucleotide binding site, each monomer also has two other binding sites, one for proteins, and one for the anti-cancer drug taxol. The assembly of tubulin and its regulation through dynamic instability results from the fine tuning of these three components. Identifying the atomic structure of tubulin's drug binding sites should prove especially valuable for cancer researchers. Taxol, a natural substance found in the bark of the Pacific yew tree, has been shown in clinical tests to be an effective treatment for a number of malignancies, including ovarian, breast, and lung.
Cancer occurs when cell division runs amok.
By binding to tubulin and causing the protein to lose its flexibility, taxol can prevent cell division from taking place. With better knowledge of the tubulin drug binding site and its interaction with taxol, scientists should be able to synthesize an even more effective anti-cancer drug, one that interacts only with the tubulin of cancerous cells. To produce their model, the Berkeley Lab researchers first polymerized tubulin proteins under the same conditions in which microtubules are formed, except for the additional presence of zinc. The zinc prevents tubulin chains from curling around into hollow fibers. Instead, the polymerized tubulin forms two-dimensional crystalline sheets that are ideal for imaging by electron crystallography.