The relationship between cobalt binding to tubulin and the stimulation of assembly.
نویسندگان
چکیده
Co(II), which induces the assembly of tubulin in the absence of associated proteins, binds to multiple sites on the protein in a low ionic strength medium. However, in the presence of concentrations of buffer and GTP used in assembly reactions, the number of sites occupied by Co(I1) is drastically reduced. At GTP and Co(I1) concentrations where the major polymerized products are broad sheets of protofilaments, about 3 Co(II) atoms are bound/tubulin dimer. Increasing the GTP concentration lowers the amount of assembly, increases the proportion of microtubules to sheets, and decreases the amount of Co(I1) bound. It is concluded that the binding of free Co(II) is necessary to stimdate assembly and the less Co(II) bound, the more likely is the formation of microtubules. Tubulin containing 1 tightly bound Co(I1) can be isolated by passing tubulin preincubated with an excess of Co(II) through phosphocellulose. Only 50% of the tight Co(I1) binding can be prevented by Mg(I1) or Mn(II), but 100% is prevented by Zn(II), Cd(II), and Cu(1). Moreover, Mg(1I) can only displace a fraction of the bound Co(I1). The Mg(I1) content of tubulin is reduced after the cobalt is bound. Tubulin containing 1 tightly bound cobalt can assemble into microtubules and sheets if either more cobalt or taxol is added. The Mg(I1) and Co(I1) contents of cold-soluble assembled products are approximately 1 atom/tubulin dimer, respectively, suggesting that the Co(II) is not situated at the Mg(I1) site and that only tubulin containing 1 Mg(II)/dimer assembles into protofilamentous structures.
منابع مشابه
Molecular Modeling Studies on Vinblastine Binding Site of Tubulin for Antimitotic agents
Medicinal chemistry depends on many other disciplines ranging from organic chemistry andpharmacology to computational chemistry. Typically medicinal chemists use the moststraightforward ways to prepare compounds. The validation of any design project comes from thebiological testing.Studies of the binding site of vinblastine by a single cross—linking experiment identified it asbeing between resi...
متن کاملAb Initio Study of Vinblastine-Tubulin Anticancer Complex
Vinblastine is an important anticancer agent known to diminish microtubule assembly. Ab initio calculations are applied to examine the structural properties and different energies of vinblastine-tubulin complex in different dielectric constants and temperatures. The aims of this work are discovery the best optimized structure and thermodynamic properties of vinblastine-tubulin complex ...
متن کاملIn Silico Screening Studies on Methanesulfonamide Derivatives as Dual Hsp27 and Tubulin Inhibitors Using QSAR and Molecular Docking
The expression of heat shock protein 27 (Hsp27) as a chaperone protein, is increased in response to various stress stimuli such as anticancer chemotherapy. This phenomenon can lead to survive of the cells and causes drug resistance. In this study, a series of methanesulfonamide derivatives as dual Hsp27 and tubulin inhibitors in the treatment of cancer were applied to quantitative structure–act...
متن کاملIn-silico Investigation of Tubulin Binding Modes of a Series of Novel Antiproliferative Spiroisoxazoline Compounds Using Docking Studies
Interference with microtubule polymerization results in cell cycle arrest leading to cell death. Colchicine is a well-known microtubule polymerization inhibitor which does so by binding to a specific site on tubulin. A set of 3',4'-bis (substituted phenyl)-4'H-spiro[indene-2,5'-isoxazol]-1(3H)-one derivatives with known antiproliferative activities were evaluated for their tubulin binding modes...
متن کاملIn-silico Investigation of Tubulin Binding Modes of a Series of Novel Antiproliferative Spiroisoxazoline Compounds Using Docking Studies
Interference with microtubule polymerization results in cell cycle arrest leading to cell death. Colchicine is a well-known microtubule polymerization inhibitor which does so by binding to a specific site on tubulin. A set of 3',4'-bis (substituted phenyl)-4'H-spiro[indene-2,5'-isoxazol]-1(3H)-one derivatives with known antiproliferative activities were evaluated for their tubulin binding modes...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- The Journal of biological chemistry
دوره 257 10 شماره
صفحات -
تاریخ انتشار 1982