EF-Tu and EF-G are activated by allosteric effects

EF-Tu and EF-G are activated by allosteric effects
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EF-Tu 和 EF-G 由变构效应激活

DOI:
10.1073/pnas.1800054115
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发表时间:
2018
期刊:
Proceedings of the National Academy of Sciences
影响因子:
--
通讯作者:
Warshel, Arieh
Warshel, Arieh
中科院分区:
--
文献类型:
--
作者:
Mondal, Dibyendu;Warshel, Arieh

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许多细胞过程是由GTP酶控制的,并且获得对这些过程的激活的定量理解一直是一个重大挑战。特别是,它是至关重要的,以获得可靠的自由能表面的相关反应路径在解决方案和GTP酶活性位点。在这里,我们重新审视能量的激活EF-G和EF-Tu的核糖体和探索的性质的催化GTdR反应。EF-Tu与EF-G的比较使我们能够探索EF-Tu可用结构的可能问题的影响。此外,突变效应被用来仔细验证新出现的结论。结果表明,该反应既可以通过双水机理进行,也可以通过单水(GTP为碱)机理进行。然而,在这两种情况下,激活涉及结构变构效应,这可能是所有GTP酶的通用激活机制。
Many cellular processes are controlled by GTPases, and gaining quantitative understanding of the activation of such processes has been a major challenge. In particular, it is crucial to obtain reliable free-energy surfaces for the relevant reaction paths both in solution and in GTPases active sites. Here, we revisit the energetics of the activation of EF-G and EF-Tu by the ribosome and explore the nature of the catalysis of the GTPase reaction. The comparison of EF-Tu to EF-G allows us to explore the impact of possible problems with the available structure of EF-Tu. Additionally, mutational effects are used for a careful validation of the emerging conclusions. It is found that the reaction may proceed by both a two-water mechanism and a one-water (GTP as a base) mechanism. However, in both cases, the activation involves a structural allosteric effect, which is likely to be a general-activation mechanism for all GTPases.
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