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. 2024 Mar 27;17(1):89.
doi: 10.1186/s13104-024-06744-5.

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

Abigail O Ayodele  1 , Brenda Udosen  1   2 , Olugbenga O Oluwagbemi  3   4 , Elijah K Oladipo  5   6 , Idowu Omotuyi  7   8 , Itunuoluwa Isewon  9 , Oyekanmi Nash  1 , Opeyemi Soremekun  2   10 , Segun Fatumo  11   12   13
Affiliations

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

Abigail O Ayodele et al. BMC Res Notes. .

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.

Keywords: O-linked N-acetylglucosamine transferase (OGT), 3 and 4; Single nucleotide polymorphism (SNPs).

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The Hexosamine Biosynthesis pathway promotes protein O-GlcNAcylation by supplying the O-GlcNAc moiety for addition and removal on nuclear and cytoplasmic proteins [13]
Fig. 2
Fig. 2
A Verify the 3D plot for the modelled protein, B Ramachandran plot showing the majority of the modelled protein’s residues in the favoured region, C The Ramachandran plot statistics provide values for the residues, D the ERRAT overall quality factor is 98.716
See this image and copyright information in PMC

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