Exceptionally large entropy contributions enable the high rates of GTP hydrolysis on the ribosome.
Exceptionally large entropy contributions enable the high rates of GTP hydrolysis on the ribosome.
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DOI：
10.1038/srep15817
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发表时间：
2015-10-26
影响因子：
4.6
通讯作者：
Kamerlin SC
中科院分区：
文献类型：
--
作者：
Åqvist J;Kamerlin SC
核糖体上的蛋白质合成涉及到在mRNA翻译周期的几个关键步骤中GTP的水解。这些步骤是由翻译的GTP酶催化的，其中伸长因子Tu(EF-Tu)是已知最快的GTP酶。在这里，我们使用广泛的计算机模拟来探索它在核糖体上极高的催化速率的来源，并表明它是由非常大的正激活熵实现的。这一熵项(TΔS‡)在25 °C时超过7 / ，这是翻译GTP酶所使用的反应机制的特征，它使这些酶的水解率超过500 S−1。这种熵驱动的机制可能反映了对蛋白质合成速度的非常高的选择压力，这使得每个单独的GTP酶的速率接近整个翻译周期的最大周转速率。
Protein synthesis on the ribosome involves hydrolysis of GTP in several key steps of the mRNA translation cycle. These steps are catalyzed by the translational GTPases of which elongation factor Tu (EF-Tu) is the fastest GTPase known. Here, we use extensive computer simulations to explore the origin of its remarkably high catalytic rate on the ribosome and show that it is made possible by a very large positive activation entropy. This entropy term (TΔS‡) amounts to more than 7 kcal/mol at 25 °C. It is further found to be characteristic of the reaction mechanism utilized by the translational, but not other, GTPases and it enables these enzymes to attain hydrolysis rates exceeding 500 s−1. This entropy driven mechanism likely reflects the very high selection pressure on the speed of protein synthesis, which drives the rate of each individual GTPase towards maximal turnover rate of the whole translation cycle.