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In Silico Investigation of AKT2 Gene and Protein Abnormalities Reveals Potential Association with Insulin Resistance and Type 2 Diabetes.

التفاصيل البيبلوغرافية
العنوان: In Silico Investigation of AKT2 Gene and Protein Abnormalities Reveals Potential Association with Insulin Resistance and Type 2 Diabetes.
المؤلفون: Elangeeb ME; Department of Basic Medical Sciences, College of Applied Medical Sciences, University of Bisha, Bisha 61922, Saudi Arabia., Elfaki I; Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk 47512, Saudi Arabia., Elkhalifa MA; Department of Anatomy, Faculty of Medicine and Health Sciences, University of Bisha, Bisha 61922, Saudi Arabia., Adam KM; Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Bisha, Bisha 61922, Saudi Arabia., Alameen AO; Department of Biomedical Science, Faculty of Veterinary Medicine, King Faisal University, Alahssa 31982, Saudi Arabia., Elfadl AK; Veterinary Research Section, Ministry of Municipality, Doha P.O. Box 35081, Qatar.; Department of Pathology, Faculty of Veterinary Medicine, University of Khartoum, Khartoum 11115, Sudan., Albalawi IA; Department of Surgical Oncology, Faculty of Medicine, University of Tabuk, Tabuk 47512, Saudi Arabia., Almasoudi KS; Department of Medical Lab Technology, Prince Fahad Bin Sultan Chair for Biomedical Research, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia., Almotairi R; Department of Medical Lab Technology, Prince Fahad Bin Sultan Chair for Biomedical Research, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia., Alsaedi BSO; Department of Statistics, University of Tabuk, Tabuk 47512, Saudi Arabia., Alhelali MH; Department of Statistics, University of Tabuk, Tabuk 47512, Saudi Arabia., Mir MM; Department of Basic Medical Sciences, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia., Amle D; Department of Biochemistry, All India Institute of Medical Sciences, Nagpur 441108, India., Mir R; Department of Medical Lab Technology, Prince Fahad Bin Sultan Chair for Biomedical Research, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia.
المصدر: Current issues in molecular biology [Curr Issues Mol Biol] 2023 Sep 12; Vol. 45 (9), pp. 7449-7475. Date of Electronic Publication: 2023 Sep 12.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 100931761 Publication Model: Electronic Cited Medium: Internet ISSN: 1467-3045 (Electronic) Linking ISSN: 14673037 NLM ISO Abbreviation: Curr Issues Mol Biol Subsets: PubMed not MEDLINE
أسماء مطبوعة: Publication: 2021- : Basel, Switzerland : MDPI
Original Publication: Wymondham, Norfolk, UK : Caister Academic Press,
مستخلص: Type 2 diabetes (T2D) develops from insulin resistance (IR) and the dysfunction of pancreatic beta cells. The AKT2 protein is very important for the protein signaling pathway, and the non-synonymous SNP (nsSNPs) in AKT2 gene may be associated with T2D. nsSNPs can result in alterations in protein stability, enzymatic activity, or binding specificity. The objective of this study was to investigate the effect of nsSNPs on the AKT2 protein structure and function that may result in the induction of IR and T2D. The study identified 20 variants that were considered to be the most deleterious based on a range of analytical tools included (SIFT, PolyPhen2, Mut-pred, SNAP2, PANTHER, PhD-SNP, SNP&Go, MUpro, Cosurf, and I-Mut). Two mutations, p.A179T and p.L183Q, were selected for further investigation based on their location within the protein as determined by PyMol. The results indicated that mutations, p.A179T and p.L183Q alter the protein stability and functional characteristics, which could potentially affect its function. In order to conduct a more in-depth analysis of these effects, a molecular dynamics simulation was performed for wildtype AKT2 and the two mutants (p.A179T and p.L183Q). The simulation evaluated various parameters, including temperature, pressure, density, RMSD, RMSF, SASA, and Region, over a period of 100 ps. According to the simulation results, the wildtype AKT2 protein demonstrated higher stability in comparison to the mutant variants. The mutations p.A179T and p.L183Q were found to cause a reduction in both protein stability and functionality. These findings underscore the significance of the effects of nsSNPs (mutations p.A179T and p.L183Q) on the structure and function of AKT2 that may lead to IR and T2D. Nevertheless, they require further verifications in future protein functional, protein-protein interaction, and large-scale case-control studies. When verified, these results will help in the identification and stratification of individuals who are at risk of IR and T2D for the purpose of prevention and treatment.
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فهرسة مساهمة: Keywords: AKT2; bioinformatics; insulin resistance; insulin signaling pathway; nsSNP; protein; type 2 diabetes
تواريخ الأحداث: Date Created: 20230927 Latest Revision: 20231003
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC10528407
DOI: 10.3390/cimb45090471
PMID: 37754255
قاعدة البيانات: MEDLINE
الوصف
تدمد:1467-3045
DOI:10.3390/cimb45090471