Crystallization of a macromolecular ring assembly of tubulin liganded with the anti-mitotic drug podophyllotoxin.
The interaction of the anti-cancer drug podophyllotoxin with a high-molecular-weight assembly of tubulin has been employed to produce three-dimensional 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 A, b = 330 A, c = 460 A, beta = 128 degrees. The basis of these crystals is ring oligomers with a molecular mass of approximately 6 x 10(6) Da. So far, the crystals diffract to 8-A resolution and a first complete data set to 12-A resolution has been collected under cryogenic conditions. The crystals grew from conventionally purified tubulin consisting of multiple isoforms and different posttranslational modifications. Thus, the use of highly homogeneous tubulin preparations should improve the diffraction quality of these crystals.
Schönbrunn
E
E
Max-Planck-Unit for Structural Molecular Biology, c/o DESY, Hamburg, 22603, Germany. eschoenb@lamar.colostate.edu
Phlippen
W
W
Trinczek
B
B
Sack
S
S
Eschenburg
S
S
Mandelkow
E M
EM
Mandelkow
E
E
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D001717:Birds; D003460:Crystallization; D004912:Erythrocytes / Q000737:chemistry; D008854:Microscopy, Electron; D011034:Podophyllotoxin / Q000737:chemistry*; D013552:Swine; D014404:Tubulin / Q000737:chemistry* / Q000648:ultrastructure; D014961:X-Ray Diffraction
D000970:Antineoplastic Agents; D014404:Tubulin; D011034:Podophyllotoxin