STUDIES ON MACROCYCLIC LACTONE ANTIBIOTICS .12. RHIZOXIN BINDING TO TUBULIN AT THE MAYTANSINE-BINDING SITE
STUDIES ON MACROCYCLIC LACTONE ANTIBIOTICS .12. RHIZOXIN BINDING TO TUBULIN AT THE MAYTANSINE-BINDING SITE
复制标题
DOI：
10.1016/0304-4165(87)90206-6
复制
发表时间：
1987-12-07
期刊：
影响因子：
--
通讯作者：
SATO, Y
中科院分区：
文献类型：
--
作者：
TAKAHASHI, M;IWASAKI, S;SATO, Y
研究了猪脑微管蛋白与有丝分裂和体外微管组装的有效抑制剂根瘤素的结合。微管蛋白每个分子具有一个根毒素结合位点，解离常数（Kd）为1.7 cntdot。10-7 M. Ansamitocin P-3是一种具有竞争性的根毒素结合抑制剂，其抑制常数为1.3。10-7 M.长春花碱对根毒素的结合也有抑制作用，但不是完全竞争，抑制常数为2.9。相比之下，根瘤素和抗菌肽P-3都是长春花碱结合的有效抑制剂。与长春碱不同的是，根瘤素抑制了tau蛋白促进的微管蛋白聚集，但即使浓度高达2 cntdot，也不会诱导微管蛋白聚集成螺旋状。此外，根瘤素强烈抑制长春花碱诱导的tau依赖性微管蛋白聚集。根毒素与微管蛋白的结合完全独立于秋水仙碱的结合。这些作用类似于美丹辛。结果表明，根毒素与美坦素结合位点结合，而根毒素与长春碱的结合位点不相同。
The binding of rhizoxin, a potent inhibitor of mitosis and in vitro microtubule assembly, to porcine brain tubulin was studied. Tubulin possesses one binding site for rhizoxin per molecule with a dissociation constant (Kd) of 1.7 .cntdot. 10-7 M. Ansamitocin P-3, a homologue of maytansine, was a competitive inhibitor of rhizoxin binding, with an inhibition constant of 1.3 .cntdot. 10-7 M. Vinblastine also inhibited rhizoxin binding, but was not fully competitive, and the inhibition constant was 2.9 .cntdot. 10-6 M. In contrast, both rhizoxin and ansamitocin P-3 were potent inhibitors of vinblastine binding. Rhizoxin inhibited tau-promoted tubulin assembly, but it, differing from vinblastine, did not induce tubulin aggregation into spirals, even at a concentration as high as 2 .cntdot. 10-5 M. In addition, rhizoxin strongly inhibited vinblastine-induced tau-dependent tubulin aggregation. Rhizoxin binding to tubulin was completely independent from colchicine binding. These effects resemble those of maytansine. The results suggested that rhizoxin binds to the maytansine-binding site and that the binding sites of rhizoxin and vinblastine are not the same.