Crystallization of a macromolecular ring assembly of tubulin liganded withthe anti-mitotic drug podophyllotoxin

The interaction of the anti-cancer drug podophyllotoxin with a high-molecul ar-weight assembly of tubulin has been employed to produce three-dimensiona l crystals from avian erythrocyte tubulin as well as from pig brain tubulin . Avian erythrocyte tubulin crystals belong to the space group C2 with unit cell dimensions a = 740 Angstrom, b = 330 Angstrom, c = 460 Angstrom, beta = 128 degrees. The basis of these crystals is ring oligomers with a molecu lar mass of approximately 6 x 10(6) Da. So far, the crystals diffract to 8- Angstrom resolution and a first complete data set to 12-Angstrom resolution has been collected under cryogenic conditions. The crystals grew from conv entionally purified tubulin consisting of multiple isoforms and different p osttranslational modifications. Thus, the use of highly homogeneous tubulin preparations should improve the diffraction quality of these crystals. (C) 1999 Academic Press.