An in-silico analysis of OGT gene association with diabetes mellitus.

Autor: Ayodele AO; H3Africa Bioinformatics Network (H3ABioNet) Node, Centre for Genomics Research and Innovation, NABDA/FMST, Abuja, Nigeria., Udosen B; H3Africa Bioinformatics Network (H3ABioNet) Node, Centre for Genomics Research and Innovation, NABDA/FMST, Abuja, Nigeria.; The African Computational Genomics (TACG) Research Group, MRC/UVRI, and LSHTM, Entebbe, Uganda., Oluwagbemi OO; Department of Computer Science and Information Technology, Faculty of Natural and Applied Sciences, Sol Plaatje University, 8301, Kimberley, South Africa.; Department of Mathematical Sciences, Stellenbosch University, 7602, Stellenbosch, South Africa., Oladipo EK; Laboratory of Molecular Biology, Immunology and Bioinformatics, Department of Microbiology, Adeleke University, 232104, Ede, Nigeria.; Genomics Unit, Helix Biogen Institute, 210214, Ogbomoso, Nigeria., Omotuyi I; Institute for Drug Research and Development, S.E. Bogoro Center, Afe Babalola University, Ado Ekiti, Nigeria.; Molecular Biology and Molecular Simulation Center (Mols&Sims), Ado Ekiti, Nigeria., Isewon I; Computer and Information Sciences Department, Covenant University, Ota, Ogun State, Nigeria., Nash O; H3Africa Bioinformatics Network (H3ABioNet) Node, Centre for Genomics Research and Innovation, NABDA/FMST, Abuja, Nigeria., Soremekun O; The African Computational Genomics (TACG) Research Group, MRC/UVRI, and LSHTM, Entebbe, Uganda.; MRC/UVRI and London School of Hygiene and Tropical Medicine London (LSHTM) Uganda Research Unit, Entebbe, Uganda., Fatumo S; H3Africa Bioinformatics Network (H3ABioNet) Node, Centre for Genomics Research and Innovation, NABDA/FMST, Abuja, Nigeria. Segun.fatumo@lshtm.ac.uk.; The African Computational Genomics (TACG) Research Group, MRC/UVRI, and LSHTM, Entebbe, Uganda. Segun.fatumo@lshtm.ac.uk.; MRC/UVRI and London School of Hygiene and Tropical Medicine London (LSHTM) Uganda Research Unit, Entebbe, Uganda. Segun.fatumo@lshtm.ac.uk.
Jazyk: angličtina
Zdroj: BMC research notes [BMC Res Notes] 2024 Mar 27; Vol. 17 (1), pp. 89. Date of Electronic Publication: 2024 Mar 27.
DOI: 10.1186/s13104-024-06744-5
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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