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Impact of deleterious mutations on structure, function and stability of serum/glucocorticoid regulated kinase 1: A gene to diseases correlation

Citation

AlAjmi, MF and Khan, S and Choudhury, A and Mohammad, T and Noor, S and Hussain, A and Lu, M and Eapen, MS and Chimankar, V and Hansbro, PM and Sohal, SS and Elasbali, AM and Hassan, MI, Impact of deleterious mutations on structure, function and stability of serum/glucocorticoid regulated kinase 1: A gene to diseases correlation, Frontiers in Molecular Biosciences, 8 pp. 1-14. ISSN 2296-889X (2021) [Refereed Article]


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DOI: doi:10.3389/fmolb.2021.780284

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.

Item Details

Item Type:Refereed Article
Keywords:lung fibrosis, cancer, COPD, neurodegeneration
Research Division:Biomedical and Clinical Sciences
Research Group:Cardiovascular medicine and haematology
Research Field:Cardiology (incl. cardiovascular diseases)
Objective Division:Health
Objective Group:Clinical health
Objective Field:Diagnosis of human diseases and conditions
UTAS Author:Lu, M (Dr Monica LU)
UTAS Author:Eapen, MS (Mr Mathew Eapen)
UTAS Author:Sohal, SS (Dr Sukhwinder Sohal)
ID Code:147618
Year Published:2021
Deposited By:Health Sciences
Deposited On:2021-11-10
Last Modified:2021-11-10
Downloads:0

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