Misakinolide A Is a Marine Macrolide That Caps but Does Not Sever Filamentous Actin*
Misakinolide A Is a Marine Macrolide That Caps but Does Not Sever Filamentous Actin*
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Misakinolide A 是一种海洋大环内酯，可覆盖但不切断丝状肌动蛋白*
DOI：
10.1074/jbc.272.12.7841
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
M. Bubb
中科院分区：
文献类型：
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作者：
David R. Terry;Ilan Spector;T. Higa;M. Bubb
我们已经调查了海洋天然产物，misakinidae A，40元二聚内酯大环内酯，不同swinholide A的大环内酯环的大小的生物化学性质。分析ultracenthagation和稳态荧光实验表明，misakinsultase A同时结合到两个肌动蛋白亚基几乎相同的亲和力swinholide A，这表明在环的大小的修改不改变肌动蛋白结合位点。沉降平衡实验表明，在每个结合位点的结合是独立的，Kd约为50 nM。值得注意的是，misakinidA并不像swinholide A那样切断肌动蛋白丝;相反，它覆盖了F-肌动蛋白的倒刺末端。当帽由misakinesterA，在倒刺端的伸长速率常数降低到零，尖端的增长只受到影响的程度，该化合物螯合未聚合的肌动蛋白。Misakinhibitor A对肌动蛋白亚基离开倒刺末端的解离速率基本上没有影响。能量最小化模型misakinoprotein A和swinholide A是一致的，在这两个分子中的相同的结合位点的保守性，但一个结合位点相对于其他的方向的差异可以解释为什么swinholide A具有切断活性，而misakinoprotein A只具有加帽活性。
We have investigated the biochemical properties of the marine natural product, misakinolide A, a 40-membered dimeric lactone macrolide that differs from swinholide A only in the size of the macrolide ring. Analytical ultracentrifugation and steady-state fluorescence experiments show that misakinolide A binds simultaneously to two actin subunits with virtually the same affinity as swinholide A, suggesting that the modification in the ring size does not change the actin-binding site. Sedimentation equilibrium experiments suggest that binding is independent at each binding site, with a Kd of approximately 50 nM. Remarkably, misakinolide A does not sever actin filaments like swinholide A; rather, it caps the barbed end of F-actin. When capped by misakinolide A, the elongation rate constant at the barbed end is reduced to zero; pointed end growth was affected only to the extent that the compound sequesters unpolymerized actin. Misakinolide A has essentially no effect on the off-rate of actin subunits leaving the barbed end. Energy-minimized models of misakinolide A and swinholide A are consistent with conservation of identical binding sites in both molecules, but a difference in orientation of one binding site relative to the other may explain why swinholide A has severing activity whereas misakinolide A only has capping activity.
凝溶胶蛋白的肌动蛋白侧结合结构域也覆盖肌动蛋白丝。
DOI：
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发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
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作者：
Sun,HQ;Wooten,DC;Janmey,PA;Yin,HL
通讯作者：
Yin,HL
弓毒毒素对细胞形态、细胞骨架组织和肌动蛋白聚合的作用。
影响因子：
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作者：
Patterson,GM;Smith,CD;Kimura,LH;Britton,BA;Carmeli,S
通讯作者：
Carmeli,S
DOI：
10.1093/jnci/87.1.46
发表时间：
1995-01-04
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
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作者：
SENDEROWICZ, AMJ;KAUR, G;DUNCAN, KLK
通讯作者：
DUNCAN, KLK