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首页> 外文期刊>Biochemistry >Vinca site agents induce structural changes in tubulin different from and antagonistic to changes induced by colchicine site agents.
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Vinca site agents induce structural changes in tubulin different from and antagonistic to changes induced by colchicine site agents.

机译：长春花（Vinca）位点剂诱导微管蛋白的结构变化，不同于秋水仙碱位点剂诱导的变化并与其对抗。

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Vinca site agents are antimicrotubule compounds that bind to the same site on tubulin as do the vinca alkaloids. These include agents that induce the formation of nonmicrotubule oligomers of tubulin (vinblastine and vincristine) and agents that do not (maytansine and rhizoxin). All of these quench the fluorescence of tubulin upon binding. Quenching preferentially affects the red side of tubulin emission, likely affecting more than one solvent-exposed tryptophan. Similar quenching is observed upon binding to either tubulin or tubulin-colchicine. None of these agents induces the local unfolding of the amphipathic helix in the carboxyl terminal region of beta-tubulin that colchicine and other colchicine site ligands do. All four vinca site agents inhibit this unfolding in tubulin-colchicine complexes without displacing colchicine. Both groups of vinca site agents enhance the chymotryptic cleavage of beta-tubulin after Tyr-281. Both groups of vinca site agents increase the beta-tubulin specificity of photolabeling with colchicine, and both groups inhibit colchicine-stimulated GTP hydrolysis. All of these effects common to both groups of vinca site agents are interpreted as due to vinca site occupancy alone. The vinca alkaloids differ from maytansine and rhizoxin by causing a large enhancement of chymotryptic cleavage of beta and a large inhibition of typtic cleavage of alpha, after Arg-339. These effects are interpreted as due to vinca induced oligomerization of tubulin. It is argued that the common binding site for the vinca site agents is located on beta-tubulin, close to the helix that is disrupted by colchicine.
机译：长春蔓定位剂是与长春花生物碱一样结合在微管蛋白上相同位点的抗微管化合物。这些包括诱导微管蛋白非微管寡聚物（长春碱和长春新碱）形成的试剂和不诱导微管蛋白的非微管寡聚物形成的试剂（美登素和根硫辛）。所有这些都在结合后淬灭了微管蛋白的荧光。淬火优先影响微管蛋白发射的红色面，可能影响不止一种溶剂暴露的色氨酸。与微管蛋白或微管蛋白秋水仙碱结合后，观察到类似的淬灭。这些物质均未诱导秋水仙碱和其他秋水仙碱位点配体在β-微管蛋白的羧基末端区域中两亲性螺旋的局部展开。所有四种长春花碱制剂均抑制微管蛋白-秋水仙碱复合物中的这种展开，而不取代秋水仙碱。两组长春花部位药剂均能增强Tyr-281后β-微管蛋白的胰凝乳酶裂解作用。两组长春花碱定位剂均增加了秋水仙碱进行光标记的β-微管蛋白特异性，并且两组均抑制了秋水仙碱刺激的GTP水解。两组长春花站点剂共有的所有这些作用均被解释为仅由于长春花站点占用。长春花生物碱与美登素和根霉毒素的不同之处在于，在Arg-339之后，导致β的胰凝乳蛋白酶切割大大增强，而α的Typical切割受到很大抑制。这些作用被解释为是由于长春花碱诱导的微管蛋白寡聚。有人认为长春花碱作用剂的共同结合位点位于β-微管蛋白上，靠近被秋水仙碱破坏的螺旋。

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