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Investigation of SGLT2 Variant Interaction with Empagliflozin and Sotagliflozin | ||
| Journal of Genetic Resources | ||
| دوره 11، شماره 2، 2025، صفحه 214-224 اصل مقاله (648.2 K) | ||
| نوع مقاله: Research Article | ||
| شناسه دیجیتال (DOI): 10.22080/jgr.2025.28953.1431 | ||
| نویسندگان | ||
| Mehdi Sadeghi* 1؛ Mobina Dayani2؛ Parviz Malekzadeh3 | ||
| 1Department of Cellular and Molecular Biology, Faculty of Sciences, Semnan University, Semnan, Iran | ||
| 2Department of Biotechnology, Faculty of New Sciences and Technologies, Semnan University, Semnan, Iran | ||
| 3Department of Biology, Faculty of Science, University of Qom, Qom, Iran | ||
| تاریخ دریافت: 19 فروردین 1404، تاریخ بازنگری: 04 خرداد 1404، تاریخ پذیرش: 22 مهر 1404 | ||
| چکیده | ||
| Postprandial hyperglycemia, a hallmark of type 2 diabetes mellitus, is often mitigated through the use of sodium-glucose co-transporter 2 (SGLT2) inhibitors, which function to lower blood glucose levels by promoting glucose excretion in the urine. Empagliflozin and sotagliflozin are examples of such inhibitors. The molecular mechanism and efficiency of these drugs on SGLT2 variants are less understood. In this study, the effectiveness of empagliflozin and sotagliflozin on the SGLT2 protein variants, including native, V95I, V157A, L283M, and F453A, has been investigated to explore the extent and mechanism of action of these drugs on the protein's function. The molecular docking technique was used to investigate the interactions between empagliflozin, sotagliflozin, and the SGLT2 protein. The three-dimensional structures of the protein and ligands were retrieved from the Protein Data Bank (PDB) and PubChem databases, respectively. Ligand structures were optimized using the Avogadro software. Molecular docking simulations were subsequently performed using AutoDock Tools and the Vina algorithm. Binding affinities and interacting amino acid residues were then analyzed. An inverse correlation was observed between binding energy and structural variation, indicating that the introduced variants negatively impacted drug performance, diminishing the efficacy of empagliflozin and sotagliflozin. Specifically, the F453A variant, characterized by a mutation in Phe453- a critical residue for ligand binding- presented the largest structural variation and lowest binding energies to the drugs (-10.1 kcal/mol for empagliflozin and -9.4 kcal/mol for sotagliflozin). This reduction in binding affinity would impede the drugs' capacity to lower blood glucose levels, thus underscoring the significance of Phe453. | ||
| کلیدواژه‌ها | ||
| Sodium-glucose co-transporter 2؛ molecular docking؛ empagliflozin؛ sotagliflozin | ||
| مراجع | ||
|
Agu, P. C., Afiukwa, C. A., Orji, O. U., Ezeh, E. M., Ofoke, I. H., Ogbu, C. O., Ugwuja, E. I., & Aja, P. M. (2023). Molecular docking as a tool for the discovery of molecular targets of nutraceuticals in diseases management. Scientific Reports, 13(1), 13398. https://doi.org/10.1038/s41598-023-40160-2
Bhattacharya, S., Asati, V., Mishra, M., Das, R., Kashaw, V., & Kashaw, S. K. (2021). Integrated computational approach on sodium-glucose co-transporter 2 (SGLT2) inhibitors for the development of novel antidiabetic agents. Journal of Molecular Structure, 1227, 129511. https://doi.org/10.1016/j.molstruc.2020.129511
Cefalo, C. M. A., Cinti, F., Moffa, S., Impronta, F., Sorice, G. P., Mezza, T., ... & Giaccari, A. (2019). Sotagliflozin, the first dual SGLT inhibitor: current outlook and perspectives. Cardiovascular Diabetology, 18(1), 20. https://doi.org/10.1186/s12933-019-0828-y
Chang, C.Y., Ho, Y., Lin, S.J., & Liu, H.L. (2019). Discovery of novel N-glycoside and non-glycoside hSGLT2 inhibitors for the treatment of type 2 diabetes mellitus. Journal of Diabetes Mellitus, 09(03), 77-104. https://doi.org/10.4236/jdm.2019.93009
Dai, Z.C., Chen, J.X., Zou, R., Liang, X.B., Tang, J.X., & Yao, C.W. (2023). Role and mechanisms of SGLT-2 inhibitors in the treatment of diabetic kidney disease. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1213473
Fitchett, D., Inzucchi, S. E., Cannon, C. P., McGuire, D. K., Scirica, B. M., Johansen, O. E., ... & Zinman, B. (2019). Empagliflozin reduced mortality and hospitalization for heart failure across the spectrum of cardiovascular risk in the EMPA-REG OUTCOME trial. Circulation, 139(11), 1384-1395. https://doi.org/10.1161/CIRCULATIONAHA.118.037778
Friedman, R. (2022). Computational studies of protein-drug binding affinity changes upon mutations in the drug target. Computational Molecular Science, 12(1), e1563. https://doi.org/10.1002/wcms.1563
Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., Uribe, K. B., ... & Martín, C. (2020). Pathophysiology of type 2 diabetes mellitus. International Journal of Molecular Sciences, 21(17), 6275. https://doi.org/10.3390/ijms21176275
Ganwir, P., Bhadane, R., & Chaturbhuj, G. U. (2024). In-silico screening and identification of glycomimetic as potential human sodium-glucose co-transporter 2 inhibitor. Computational Biology and Chemistry, 110, 108074. https://doi.org/10.1016/j.compbiolchem.2024.108074
García-Heredia, J. M., Otero-Albiol, D., Pérez, M., Pérez-Castejón, E., Muñoz-Galván, S., & Carnero, A. (2020). Breast tumor cells promotes the horizontal propagation of EMT, stemness, and metastasis by transferring the MAP17 protein between subsets of neoplastic cells. Oncogenesis, 9(10), 96. https://doi.org/10.1038/s41389-020-00280-0
Hiraizumi, M., Akashi, T., Murasaki, K., Kishida, H., Kumanomidou, T., Torimoto, N., Nureki, O., & Miyaguchi, I. (2024). Transport and inhibition mechanism of the human SGLT2-MAP17 glucose transporter. Nature Structural and Molecular Biology, 31(1), 159-169. https://doi.org/10.1038/s41594-023-01134-0
Home, P. (2019). Cardiovascular outcome trials of glucose-lowering medications: an update. Diabetologia, 62(3), 357-369. https://doi.org/10.1007/s00125-018-4801-1
Hotait, Z. S., Lo Cascio, J. N., Choos, E. N. D., & Shepard, B. D. (2022). The role of the renal proximal tubule in glucose homeostasis. American Journal of Physiology, 323(3), 791-803. https://doi.org/10.1152/ajpcell.00225.2022
Hsia, D. S., Grove, O., & Cefalu, W. T. (2017). An update on sodium-glucose co-transporter-2 inhibitors for the treatment of diabetes mellitus. Diabetes and Obesity, 24(1), 73-79. https://doi.org/10.1097/MED.0000000000000311
Kaur, P., Behera, B. S., Singh, S., & Munshi, A. (2021). The pharmacological profile of SGLT2 inhibitors: Focus on mechanistic aspects and pharmacogenomics. European Journal of Pharmacology, 904, 174169. https://doi.org/10.1016/j.ejphar.2021.174169
Lahti, J. L., Tang, G. W., Capriotti, E., Liu, T., & Altman, R. B. (2012). Bioinformatics and variability in drug response: a protein structural perspective. Journal of the Royal Society Interface, 9(72), 1409-1437. https://doi.org/10.1098/rsif.2011.0843
Maccari, R., & Ottanà, R. (2022). Sodium-glucose cotransporter inhibitors as antidiabetic drugs: Current development and future perspectives. Journal of Medicinal Chemistry, 65(16), 10848-10881. https://doi.org/10.1021/acs.jmedchem.2c00867
Mahaffey, K. W., Neal, B., Perkovic, V., de Zeeuw, D., Fulcher, G., Erondu, N., ... & Matthews, D. R. (2018). Canagliflozin for primary and secondary prevention of cardiovascular events: results from the CANVAS program (Canagliflozin Cardiovascular Assessment Study). Circulation, 137(4), 323-334. https://doi.org/10.1161/CIRCULATIONAHA.117.032038
Mashraqi, M. M., Chaturvedi, N., Alam, Q., Alshamrani, S., Bahnass, M. M., Ahmad, K., ... & Rizvi, S. M. D. (2021). Biocomputational prediction approach targeting FimH by natural SGLT2 inhibitors: A possible way to overcome the uropathogenic effect of SGLT2 inhibitor drugs. Molecules, 26(3), 582. https://doi.org/10.3390/molecules26030582
Mordarska, K., & Godziejewska-Zawada, M. (2017). Diabetes in the elderly. Menopausal Review, 2, 38-43. https://doi.org/10.5114/pm.2017.68589
Nishiyama, A., & Kitada, K. (2023). Possible renoprotective mechanisms of SGLT2 inhibitors. Frontiers in Medicine, 10, 1115413. https://doi.org/10.3389/fmed.2023.1115413
Niu, Y., Liu, R., Guan, C., Zhang, Y., Chen, Z., Hoerer, S., ... & Chen, L. (2022). Structural basis of inhibition of the human SGLT2-MAP17 glucose transporter. Nature, 601(7892), 280-284. https://doi.org/10.1038/s41586-021-04212-9
Nuffer, W., Williams, B., & Trujillo, J. M. (2019). A review of sotagliflozin for use in type 1 diabetes. Therapeutic Advances in Endocrinology and Metabolism, 10, 2042018819890527 https://doi.org/10.1177/2042018819890527
Prasetiyo, A., Mumpuni, E., Luthfiana, D., Herowati, R., & Putra, G. S. (2025). In silico discovery of potential sodium-glucose cotransporter-2 (SGLT-2) inhibitors from Smallanthus sonchifolius (Poepp.) H.Rob. via molecular docking and molecular dynamics simulation approach. Journal of Pharmacy and Pharmacognosy Research, 13(3), 716-728. https://doi.org/10.56499/jppres24.2104_13.3.716
Wan, S., Kumar, D., Ilyin, V., Al Homsi, U., Sher, G., Knuth, A., & Coveney, P. V. (2021). The effect of protein mutations on drug binding suggests ensuing personalised drug selection. Scientific Reports, 11(1), 13452. https://doi.org/10.1038/s41598-021-92785-w
Xu, B., Li, S., Kang, B., & Zhou, J. (2022). The current role of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes mellitus management. Cardiovascular Diabetology, 21(1), 83. https://doi.org/10.1186/s12933-022-01512-w | ||
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