ArticleJournal of chemical information and modeling2020
Kinase Activation by Small Conformational Changes.
Article in Journal of chemical information and modeling, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
10 citing papers in PubMed, 24 citations in OpenAlex.
- Networked salt-bridges mediate magnesium-dependent conformational dynamics and functional regulation in type IA topoisomerases.Nature communications · 2026Article
- VIK-Mediated Auxin Signaling Regulates Lateral Root Development in Arabidopsis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Activation Loop Plasticity and Active Site Coupling in the MAP Kinase, ERK2.Journal of molecular biology · 2023Article
- Analysis of Structural Changes in the Protein near the Phosphorylation Site.Biomolecules · 2023Article
- Navigating the ERK1/2 MAPK Cascade.Biomolecules · 2023Review
- Development of a cell-free screening assay for the identification of direct PERK activators.PloS one · 2023Article
- Dynamic equilibria in protein kinases.Current opinion in structural biology · 2021Review
- TYROSINE KINASES: COMPLEX MOLECULAR SYSTEMS CHALLENGING COMPUTATIONAL METHODOLOGIES.The European physical journal. B · 2021Article
- Activation Loop Dynamics Are Coupled to Core Motions in Extracellular Signal-Regulated Kinase-2.Biochemistry · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Protein kinases (PKs) are allosteric enzymes that play an essential role in signal transduction by regulating a variety of key cellular processes. Most PKs suffer conformational rearrangements upon phosphorylation that strongly enhance the catalytic activity. Generally, it involves the movement of the phosphorylated loop toward the active site and the rotation of the whole C-terminal lobe. However, not all kinases undergo such a large configurational change: The MAPK extracellular signal-regulated protein kinases ERK1 and ERK2 achieve a 50 000 fold increase in kinase activity with only a small motion of the C-terminal region. In the present work, we used a combination of molecular simulation tools to characterize the conformational landscape of ERK2 in the active (phosphorylated) and inactive (unphosphorylated) states in solution in agreement with NMR experiments. We show that the chemical reaction barrier is strongly dependent on ATP conformation and that the "active" low-barrier configuration is subtly regulated by phosphorylation, which stabilizes a key salt bridge between the conserved Lys52 and Glu69 belonging to helix-C and promotes binding of a second Mg ion. Our study highlights that the on-off switch embedded in the kinase fold can be regulated by small, medium, and large conformational changes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.