The length of the bound fatty acid influences the dynamics of the acyl carrier protein and the stability of the thioester bond.
The length of the bound fatty acid influences the dynamics of the acyl carrier protein and the stability of the thioester bond.
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DOI：
10.1021/bi9014659
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发表时间：
2010-01-26
期刊：
影响因子：
2.9
通讯作者：
Markley, John L.
中科院分区：
文献类型：
--
作者：
Zornetzer, Gregory A.;Tanem, Justinn;Fox, Brian G.;Markley, John L.
参与脂肪酸生物合成的酰基载体蛋白已显示出高度的构象灵活性，因为它们能够螯合长度为4至18个碳的脂肪酸中间体。这种灵活性已经在连接到不同脂肪酸的酰基载体蛋白的X射线和NMR结构中观察到。比较癸酰基-ACP和硬脂酰基-ACP的NMR研究表明，ACP在与较长的脂肪酸结合时表现出更强的动态运动。我们已经使用了互补的化学和NMR方法作为一种方法，以提高我们的理解的影响，脂肪酸长度的酰基载体蛋白的动力学。酰基硫酯对溶剂的可及性的化学测定揭示了链长和水解速率之间的正相关性。令人惊讶的是，这种线性相关是双相的，对于长于15个碳的脂肪酸观察到加速水解。为了进一步了解与这种加速度相关的运动，我们收集了14：0-、15：0-和16：0-ACP的15 N弛豫色散数据。形成脂肪酸结合口袋入口的残基表现出最大的分散。此外，观察到这些分散体随着脂肪酸的长度而增加。由于汇率来自拟合的数据，以两个国家的模型不同的残留物，一个更复杂的运动模型似乎需要充分解释的动态。因此，酰基-ACP提供了一个有趣的系统，为未来的调查复杂的蛋白质运动的微米和毫秒的时间尺度。
Acyl carrier proteins involved in fatty acid biosynthesis have been shown to exhibit a high degree of conformational flexibility, in that they are able to sequester fatty acid intermediates between 4 and 18 carbons in length. This flexibility has been observed in X-ray and NMR structures of acyl carrier proteins attached to different fatty acids. NMR studies comparing decanoyl-ACP and stearoyl-ACP indicated that ACP exhibits more dynamic motions when bound to longer fatty acids. We have used complementary chemical and NMR methods as an approach to improving our understanding of the effect of fatty acid length on the dynamics of acyl carrier protein. A chemical assay of the accessibility of the acyl thioester to solvent revealed a positive correlation between chain length and rate of hydrolysis. Surprisingly, this linear correlation was biphasic, with accelerated hydrolysis observed for fatty acids longer than 15 carbons. To further understand the motions associated with this acceleration, we collected 15N relaxation dispersion data for 14:0-, 15:0-, and 16:0-ACP. The greatest dispersions were exhibited by residues that form the entrance to the fatty acid binding pocket. In addition, these dispersions were observed to increase with the length of the fatty acid. Because the exchange rates derived from fitting the data to a two-state model varied from residue to residue, a more complex motional model appears to be required to adequately explain the dynamics. Thus, acyl-ACP offers an interesting system for future investigations of complex protein motions on the micro- and millisecond time scales.
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