Developing a Molecular Model to Explain the Role of O-GlcNAc Transferase (OGT) in O- GlcNAcylation

O-GlcNAcylation is a post-translational modification similar in importance to the mechanism of phosphorylation in its ability to affect signal transduction. This process is mediated by the enzyme, O- GlcNAc transferase (OGT). OGT catalyzes the addition of the sugar, N-acetylglucosamine (GlcNAc) from the carrier molecule uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) to certain serine or threonine residues in more than a thousand target substrate proteins. The TAB1 (transforming growth factor-beta-activated kinase 1 binding protein) substrate was fused to OGT. GlcNAc was shown binding to three serine residues in TAB1. Six tetratricopeptide (TPR) repeats were identified. These alpha helical paired repeats fold together to produce a single domain called the TPR domain near the N terminus of OGT. Within the TPR domain, five asparagine (Asp) residues were identified that are involved in holding the substrate in place. Beta sheets in OGT were also indicated. If TAB1 does not receive GlcNAc, it will not be able to signal the proper response of the innate immune system. This work was funded in part by NSF-DUE 1725940 for the CREST (Connecting Researchers, Educators, and STudents) Project. Developing 3-D molecular models in this way is a relatively inexpensive process to visually represent important biological relationships that can be useful when trying to understand and explain complex molecular pathways