Impact of Deleterious Mutations on Structure, Function and Stability of Serum/Glucocorticoid Regulated Kinase 1: A Gene to Diseases Correlation.
deleterious mutations
essential dynamics
molecular dynamics simulation
serum/glucocorticoid regulated kinase 1
single amino acid substitutions
Journal
Frontiers in molecular biosciences
ISSN: 2296-889X
Titre abrégé: Front Mol Biosci
Pays: Switzerland
ID NLM: 101653173
Informations de publication
Date de publication:
2021
2021
Historique:
received:
24
09
2021
accepted:
19
10
2021
entrez:
22
11
2021
pubmed:
23
11
2021
medline:
23
11
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34805284
doi: 10.3389/fmolb.2021.780284
pii: 780284
pmc: PMC8597711
doi:
Types de publication
Journal Article
Langues
eng
Pagination
780284Informations de copyright
Copyright © 2021 AlAjmi, Khan, Choudhury, Mohammad, Noor, Hussain, Lu, Eapen, Chimankar, Hansbro, Sohal, Elasbali and Hassan.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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