ArticleThe Journal of biological chemistry2018
The protonation states of GTP and GppNHp in Ras proteins.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Who cites it
8 citing papers in PubMed, 18 citations in OpenAlex.
- A Reversible ATR-FTIR Biosensor with Single-Residue Sensitivity.Analytical chemistry · 2026Article
- Assessing the mechanism of fast-cycling cancer-associated mutations of Rac1 small Rho GTPase.Protein science : a publication of the Protein Society · 2024Article
- Far-reaching effects of tyrosine64 phosphorylation on Ras revealed with BeFCommunications chemistry · 2024Article
- Mechanism-Based Redesign of GAP to Activate Oncogenic Ras.Journal of the American Chemical Society · 2023Article
- Common Mechanism of Activated Catalysis in P-loop Fold Nucleoside Triphosphatases-United in Diversity.Biomolecules · 2022Article
- Membrane-bound KRAS approximates an entropic ensemble of configurations.Biophysical journal · 2021Article
- Article
- Recent Advances in Understanding Biological GTP Hydrolysis through Molecular Simulation.ACS omega · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The small GTPase Ras transmits signals in a variety of cellular signaling pathways, most prominently in cell proliferation. GTP hydrolysis in the active center of Ras acts as a prototype for many GTPases and is the key to the understanding of several diseases, including cancer. Therefore, Ras has been the focus of intense research over the last decades. A recent neutron diffraction crystal structure of Ras indicated a protonated γ-guanylyl imidodiphosphate (γ-GppNHp) group, which has put the protonation state of GTP in question. A possible protonation of GTP was not considered in previously published mechanistic studies. To determine the detailed prehydrolysis state of Ras, we calculated infrared and NMR spectra from quantum mechanics/molecular mechanics (QM/MM) simulations and compared them with those from previous studies. Furthermore, we measured infrared spectra of GTP and several GTP analogs bound to lipidated Ras on a membrane system under near-native conditions. Our findings unify results from previous studies and indicate a structural model confirming the hypothesis that γ-GTP is fully deprotonated in the prehydrolysis state of Ras.
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