Differential effects of colchicine and its B-ring modified analog MTPT on the assembly-independent GTPase activity of purified beta-tubulin isoforms from bovine brain.
Tubulin occurs as several isoforms whose physiological significance is not clear. The binding of colchicine to tubulin inhibits its assembly and is associated with a stimulation of the intrinsic GTPase activity of tubulin. In an effort to study the conformational states of different beta-tubulin isoforms in the drug-bound form, the intrinsic GTPase activity was studied in the presence of colchicine and its B-ring-modified analog MTPT. The results show that the GTPase activities of alpha beta II, alpha beta III, and alpha beta IV are 3.1, 2.8, and 2.6 nmole/h/ml. In the presence of colchicine, the values were increased to 4.5, 9.6, and 3 nmole/h/ml for alpha beta II, alpha beta III, and alpha beta IV respectively. In the case of MTPT, which lacks the B-ring, the GTPase activities were 5.8, 11.5, and 7.3 nmole/h/ml, respectively, for alpha beta II, alpha beta III, and alpha beta IV. The results show that the B-ring of colchicine contributes differentially to the conformational changes in the beta-tubulin isoforms.
Banerjee
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Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284-7760, USA.
D000818:Animals; D001923:Brain Chemistry; D002417:Cattle; D003078:Colchicine / Q000031:analogs & derivatives / Q000494:pharmacology*; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors*; D014334:Tropolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators
D014404:Tubulin; D050257:Tubulin Modulators; C030370:2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone; D014334:Tropolone; D020558:GTP Phosphohydrolases; D003078:Colchicine