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

ABSTRACT: 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.

SUBMITTER: Mondal D

PROVIDER: S-EPMC5879710 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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

Mondal Dibyendu D Warshel Arieh A

Proceedings of the National Academy of Sciences of the United States of America 20180312 13

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 explor ...[more]

PMID: 29531062

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