ArticleBiochemistry2020
Activation Loop Dynamics Are Coupled to Core Motions in Extracellular Signal-Regulated Kinase-2.
Article in Biochemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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
18 citing papers in PubMed, 29 citations in OpenAlex.
- Streptococcus pneumoniae HtrA is a dynamic and monomeric virulence factor capable of forming larger oligomeric complexes.Protein science : a publication of the Protein Society · 2026Article
- A Foundational Shift in Models for Enzyme Function.Journal of the American Chemical Society · 2025Review
- Identifying and controlling inactive and active conformations of a serine protease.Science advances · 2025Article
- Dual-action kinase inhibitors influence p38α MAP kinase dephosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Streptococcus pneumoniae GAPN is a key metabolic player necessary for host infection.Protein science : a publication of the Protein Society · 2025Article
- Article
- Conformation selection by ATP-competitive inhibitors and allosteric communication in ERK2.eLife · 2024Article
- Allo-targeting of the kinase domain: Insights from in silico studies and comparison with experiments.Current opinion in structural biology · 2024Review
- Activation Loop Plasticity and Active Site Coupling in the MAP Kinase, ERK2.Journal of molecular biology · 2023Article
- Conformation Selection by ATP-competitive Inhibitors and Allosteric Communication in ERK2.bioRxiv : the preprint server for biology · 2023Article
- Navigating the ERK1/2 MAPK Cascade.Biomolecules · 2023Review
- Identifying structural and dynamic changes during the Biliverdin Reductase B catalytic cycle.Frontiers in molecular biosciences · 2023Article
- A substrate-induced gating mechanism is conserved among Gram-positive IgA1 metalloproteases.Communications biology · 2022Article
- ATP-competitive inhibitors modulate the substrate binding cooperativity of a kinase by altering its conformational entropy.Science advances · 2022Article
- Molecular dynamics simulations of the conformational plasticity in the active pocket of salt-inducible kinase 2 (SIK2) multi-state binding with bosutinib.Computational and structural biotechnology journal · 2022Article
- Dynamic equilibria in protein kinases.Current opinion in structural biology · 2021Review
- The high catalytic rate of the cold-active Vibrio alkaline phosphatase requires a hydrogen bonding network involving a large interface loop.FEBS open bio · 2021Article
- Cooperative dynamics across distinct structural elements regulate PTP1B activity.The Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The activation loop segment in protein kinases is a common site for regulatory phosphorylation. In extracellular signal-regulated kinase 2 (ERK2), dual phosphorylation and conformational rearrangement of the activation loop accompany enzyme activation. X-ray structures show the active conformation to be stabilized by multiple ion pair interactions between phosphorylated threonine and tyrosine residues in the loop and six arginine residues in the kinase core. Despite the extensive salt bridge network, nuclear magnetic resonance Carr-Purcell-Meiboom-Gill relaxation dispersion experiments show that the phosphorylated activation loop is conformationally mobile on a microsecond to millisecond time scale. The dynamics of the loop match those of previously reported global exchange within the kinase core region and surrounding the catalytic site that have been found to facilitate productive nucleotide binding. Mutations in the core region that alter these global motions also alter the dynamics of the activation loop. Conversely, mutations in the activation loop perturb the global exchange within the kinase core. Together, these findings provide evidence for coupling between motions in the activation loop and those surrounding the catalytic site in the active state of the kinase. Thus, the activation loop segment in dual-phosphorylated ERK2 is not held statically in the active X-ray conformation but instead undergoes exchange between conformers separated by a small energetic barrier, serving as part of a dynamic allosteric network controlling nucleotide binding and catalytic function.
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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.