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Impact of Deleterious Mutations on Structure, Function and Stability of Serum/Glucocorticoid Regulated Kinase 1: A Gene to Diseases Correlation
- Source :
- Frontiers in Molecular Biosciences, Vol 8 (2021), Frontiers in Molecular Biosciences
- Publication Year :
- 2021
- Publisher :
- Frontiers Media S.A., 2021.
-
Abstract
- Serum and glucocorticoid-regulated kinase 1 (SGK1) is a Ser/Thr protein kinase involved in regulating cell survival, growth, proliferation, and migration. Its elevated expression and dysfunction are reported in breast, prostate, hepatocellular, lung adenoma, and renal carcinomas. We have analyzed the SGK1 mutations to explore their impact at the sequence and structure level by utilizing state-of-the-art computational approaches. Several pathogenic and destabilizing mutations were identified based on their impact on SGK1 and analyzed in detail. Three amino acid substitutions, K127M, T256A, and Y298A, in the kinase domain of SGK1 were identified and incorporated structurally into original coordinates of SGK1 to explore their time evolution impact using all-atom molecular dynamic (MD) simulations for 200 ns. MD results indicate substantial conformational alterations in SGK1, thus its functional loss, particularly upon T256A mutation. This study provides meaningful insights into SGK1 dysfunction upon mutation, leading to disease progression, including cancer, and neurodegeneration.
- Subjects :
- essential dynamics
serum/glucocorticoid regulated kinase 1
QH301-705.5
deleterious mutations
Biology
medicine.disease_cause
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Biochemistry
medicine
Molecular Biosciences
Biology (General)
Protein kinase A
Molecular Biology
Gene
Original Research
Mutation
Kinase
urogenital system
Neurodegeneration
Cancer
medicine.disease
molecular dynamics simulation
Protein kinase domain
SGK1
Cancer research
single amino acid substitutions
Subjects
Details
- Language :
- English
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Frontiers in Molecular Biosciences
- Accession number :
- edsair.doi.dedup.....88cce9ff23ce9e6129799fac13dfc1af