ArticlePloS one2013
Cancer associated E17K mutation causes rapid conformational drift in AKT1 pleckstrin homology (PH) domain.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Effect of AKT1 (p. E17K) Hotspot Mutation on Malignant Tumorigenesis and Prognosis.Frontiers in cell and developmental biology · 2020Pooled it
- Single-Cell Analysis Reveals STARD10 as a Fatty Acid Metabolism Regulator of Breast Cancer Progression via the PI3K/Akt Pathway.International journal of molecular sciences · 2026Article
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- In-silico inquest reveal the efficacy ofIn silico pharmacology · 2025Article
- Multiomics Analysis of the PHLDA Gene Family in Different Cancers and Their Clinical Prognostic Value.Current issues in molecular biology · 2024Article
- PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer.Molecular cancer · 2023Review
- CSNK1G2-AS1 promotes metastasis, colony formation and serves as a biomarker in testicular germ cell tumor cells.Journal of Cancer · 2023Article
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- Molecular Dynamics Simulation and Essential Dynamics of Deleterious Proline 12 Alanine Single-Nucleotide Polymorphism in PPARPPAR research · 2022Article
- Emergence of mTOR mutation as an acquired resistance mechanism to AKT inhibition, and subsequent response to mTORC1/2 inhibition.NPJ precision oncology · 2021Article
- Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Anticancer Activity of Triazolo-Thiadiazole Derivatives and Inhibition of AKT1 and AKT2 Activation.Pharmaceutics · 2021Article
- Characterization of AKT Somatic Mutations in Chinese Breast Cancer Patients.Cancer management and research · 2021Article
- Computational Analysis of Gly482Ser Single-Nucleotide Polymorphism in PPARGC1A Gene Associated with CAD, NAFLD, T2DM, Obesity, Hypertension, and Metabolic Diseases.PPAR research · 2021Article
- In silico pathway analysis based on chromosomal instability in breast cancer patients.BMC medical genomics · 2020Article
- Development and characterization of protein kinase B/AKT isoform-specific nanobodies.PloS one · 2020Article
- Patient-Driven Discovery, Therapeutic Targeting, and Post-Clinical Validation of a NovelCancer discovery · 2019Article
- SMYD3-mediated lysine methylation in the PH domain is critical for activation of AKT1.Oncotarget · 2016Article
- AKT in cancer: new molecular insights and advances in drug development.British journal of clinical pharmacology · 2016Review
- AKT1 and BRAF mutations in pediatric aggressive fibromatosis.Cancer medicine · 2016Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAKT1 (v-akt murine thymoma viral oncogene homologue 1) kinase is one of the most frequently activated proliferated and survival pathway of cancer. Recently it has been shown that E17K mutation in the Pleckstrin Homology (PH) domain of AKT1 protein leads to cancer by amplifying the phosphorylation and membrane localization of protein. The mutant has shown resistance to AKT1/2 inhibitor VIII drug molecule. In this study we have demonstrated the detailed structural and molecular consequences associated with the activity regulation of mutant protein.
methodsThe docking score exhibited significant loss in the interaction affinity to AKT1/2 inhibitor VIII drug molecule. Furthermore, the molecular dynamics simulation studies presented an evidence of rapid conformational drift observed in mutant structure.
resultsThere was no stability loss in mutant as compared to native structure and the major cation-π interactions were also shown to be retained. Moreover, the active residues involved in membrane localization of protein exhibited significant rise in NHbonds formation in mutant. The rise in NHbond formation in active residues accounts for the 4-fold increase in the membrane localization potential of protein.
conclusionThe overall result suggested that, although the mutation did not induce any stability loss in structure, the associated pathological consequences might have occurred due to the rapid conformational drifts observed in the mutant AKT1 PH domain. GENERAL SIGNIFICANCE: The methodology implemented and the results obtained in this work will facilitate in determining the core molecular mechanisms of cancer-associated mutations and in designing their potential drug inhibitors.
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