ArticleStructure (London, England : 1993)2015
The Mechanism of ATP-Dependent Allosteric Protection of Akt Kinase Phosphorylation.
Article in Structure (London, England : 1993), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 67 citations in OpenAlex.
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- Structural insights of AKT and its activation mechanism for drug development.Molecular diversity · 2025Review
- Urolithin A suppressed osteosarcoma cell migration and invasion via targeting MMPs and AKT1.Scientific reports · 2025Article
- USP4 promotes PTC progression by stabilizing LDHA and activating the MAPK and AKT signaling pathway.Aging · 2024Article
- Targeting POLRMT by IMT1 inhibits colorectal cancer cell growth.Cell death & disease · 2024Article
- Structural investigation of Trypanosoma cruzi Akt-like kinase as drug target against Chagas disease.Scientific reports · 2024Article
- Altered Metabolism and Inflammation Driven by Post-translational Modifications in Intervertebral Disc Degeneration.Research (Washington, D.C.) · 2024Article
- Comparative Atomistic Insights on Apo and ATP-I1171N/S/T in Nonsmall-Cell Lung Cancer.ACS omega · 2023Article
- Article
- AlloReverse: multiscale understanding among hierarchical allosteric regulations.Nucleic acids research · 2023Article
- Molecular docking appraisal ofIn silico pharmacology · 2023Article
- Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19.International journal of molecular sciences · 2022Review
- Melatonin: Regulation of Biomolecular Condensates in Neurodegenerative Disorders.Antioxidants (Basel, Switzerland) · 2021Review
- Structure of autoinhibited Akt1 reveals mechanism of PIPProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Defective internal allosteric network imparts dysfunctional ATP/substrate-binding cooperativity in oncogenic chimera of protein kinase A.Communications biology · 2021Article
- Conformational Selection Mechanism Provides Structural Insights into the Optimization of APC-Asef Inhibitors.Molecules (Basel, Switzerland) · 2021Article
- Akt Is S-Palmitoylated: A New Layer of Regulation for Akt.Frontiers in cell and developmental biology · 2021Article
- Control of Akt activity and substrate phosphorylation in cells.IUBMB life · 2020Review
- Oncogenic G12D mutation alters local conformations and dynamics of K-Ras.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 4 countries.
Funding
Abstract
Kinases use ATP to phosphorylate substrates; recent findings underscore the additional regulatory roles of ATP. Here, we propose a mechanism for allosteric regulation of Akt1 kinase phosphorylation by ATP. Our 4.7-μs molecular dynamics simulations of Akt1 and its mutants in the ATP/ADP bound/unbound states revealed that ATP occupancy of the ATP-binding site stabilizes the closed conformation, allosterically protecting pT308 by restraining phosphatase access and key interconnected residues on the ATP→pT308 allosteric pathway. Following ATP→ADP hydrolysis, pT308 is exposed and readily dephosphorylated. Site-directed mutagenesis validated these predictions and indicated that the mutations do not impair PDK1 and PP2A phosphatase recruitment. We further probed the function of residues around pT308 at the atomic level, and predicted and experimentally confirmed that Akt1(H194R/R273H) double mutant rescues pathology-related Akt1(R273H). Analysis of classical Akt homologs suggests that this mechanism can provide a general model of allosteric kinase regulation by ATP; as such, it offers a potential avenue for allosteric drug discovery.
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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.