Water Molecules in the Nucleotide Binding Cleft of Actin: Effects on Subunit Conformation and Implications for ATP Hydrolysis
Water Molecules in the Nucleotide Binding Cleft of Actin: Effects on Subunit Conformation and Implications for ATP Hydrolysis
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DOI：
10.1016/j.jmb.2011.07.068
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发表时间：
2011-10-14
影响因子：
5.6
通讯作者：
Voth, Gregory A.
中科院分区：
文献类型：
--
作者：
Saunders, Marissa G.;Voth, Gregory A.
在单体肌动蛋白晶体结构中，一个高度组织化的水网络的位置在活性位点内清晰可见。然而，最近提出的丝状肌动蛋白（F-actin）模型并没有扩展到包括这些水域。由于水网络对ATP水解很重要，因此关于水位置的信息对于理解在细丝形成过程中催化速率的增加至关重要。在这里，我们发现活性位点中的水对于子域间的旋转灵活性是必不可少的，并且它们组织了活性位点结构。在模拟设置过程中包括晶体结构水，使我们能够观察到肌动蛋白亚基变平后活性位点结构的明显变化，正如Oda模型中提出的f -肌动蛋白。我们确定了相对于磷酸盐尾部的蛋白质位置和水位置的变化，这表明Factin中通过稳定β -磷酸盐上的电荷和促进催化水的去质子化来加速核苷酸水解速率的机制。(C) 2011 Elsevier Ltd.版权所有。
In the monomeric actin crystal structure, the positions of a highly organized network of waters are clearly visible within the active site. However, the recently proposed models of filamentous actin (F-actin) did not extend to including these waters. Since the water network is important for ATP hydrolysis, information about water position is critical to understanding the increased rate of catalysis upon filament formation. Here, we show that waters in the active site are essential for intersubdomain rotational flexibility and that they organize the active-site structure. Including the crystal structure waters during simulation setup allows us to observe distinct changes in the active-site structure upon the flattening of the actin subunit, as proposed in the Oda model for F-actin. We identify changes in both protein position and water position relative to the phosphate tail that suggest a mechanism for accelerating the rate of nucleotide hydrolysis in Factin by stabilizing charge on the beta-phosphate and by facilitating deprotonation of catalytic water. (C) 2011 Elsevier Ltd. All rights reserved.