Ayodele, Abigail O. and Udosen, Brenda and Oluwagbemi, Olugbenga and Oladipo, E. K. and Omotuyi, Idowu Olapos and Isewon, Itunuoluwa and Nashiru, Oyekanmi and Soremekun, Opeyemi S. and Fatumo, Segun (2024) An in-silico analysis of OGT gene association with diabetes mellitus. BMC Research Notes, 17 (89). pp. 1-8.
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Abstract
O-GlcNAcylation is a nutrient-sensing post-translational modification process. This cycling process involves two primary proteins: the O-linked N-acetylglucosamine transferase (OGT) catalysing the addition, and the glycoside hydrolase OGA (O-GlcNAcase) catalysing the removal of the O-GlCNAc moiety on nucleocytoplasmic proteins. This process is necessary for various critical cellular functions. The O-linked N-acetylglucosamine transferase (OGT) gene produces the OGT protein. Several studies have shown the overexpression of this protein to have biological implications in metabolic diseases like cancer and diabetes mellitus (DM). This study retrieved 159 SNPs with clinical significance from the SNPs database. We probed the functional effects, stability profile, and evolutionary conservation of these to determine their fit for this research. We then identified 7 SNPs (G103R, N196K, Y228H, R250C, G341V, L367F, and C845S) with predicted deleterious effects across the four tools used (PhD-SNPs, SNPs&Go, PROVEAN, and PolyPhen2). Proceeding with this, we used ROBETTA, a homology modelling tool, to model the proteins with these point mutations and carried out a structural bioinformatics method– molecular docking– using the Glide model of the Schrodinger Maestro suite. We used a previously reported inhibitor of OGT, OSMI-1, as the ligand for these mutated protein models. As a result, very good binding affinities and interactions were observed between this ligand and the active site residues within 4Å of OGT. We conclude that these mutation points may be used for further downstream analysis as drug targets for treating diabetes mellitus.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Single nucleotide polymorphism (SNPs), O-linked N-acetylglucosamine transferase (OGT), 3 and 4 |
| Subjects: | Q Science > QA Mathematics > QA76 Computer software Q Science > QH Natural history > QH301 Biology |
| Divisions: | Faculty of Engineering, Science and Mathematics > School of Electronics and Computer Science |
| Depositing User: | Patricia Nwokealisi |
| Date Deposited: | 01 Aug 2024 13:50 |
| Last Modified: | 01 Aug 2024 13:50 |
| URI: | http://eprints.covenantuniversity.edu.ng/id/eprint/18346 |
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