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


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AlAjmi, MF, Khan, S, Choudhury, A, Mohammad, T, Noor, S, Hussain, A, Lu, M ORCID: 0000-0003-1550-2276, Eapen, MS ORCID: 0000-0003-0570-7059, Chimankar, V, Hansbro, PM, Sohal, SS ORCID: 0000-0001-9627-6498, Elasbali, AM and Hassan, MI 2021 , 'Impact of deleterious mutations on structure, function and stability of serum/glucocorticoid regulated kinase 1: A gene to diseases correlation' , Frontiers in Molecular Biosciences, vol. 8 , pp. 1-14 , doi: 10.3389/fmolb.2021.780284.

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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 Type: Article
Authors/Creators: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
Keywords: lung fibrosis, cancer, COPD, neurodegeneration
Journal or Publication Title: Frontiers in Molecular Biosciences
Publisher: Frontiers Research Foundation
ISSN: 2296-889X
DOI / ID Number: 10.3389/fmolb.2021.780284
Copyright Information:

Copyright © 2021 AlAjmi, Khan, Choudhury, Mohammad, Noor, Hussain, Lu,Eapen, Chimankar, Hansbro, Sohal, Elasbali and Hassan. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) License ( The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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