Structure-Based Insight on the Mechanism of N-Glycosylation Inhibition by Tunicamycin

N-glycosylation, a common post-translational modification, is widely acknowledged to have a significant effect on protein stability and folding. N-glycosylation is a complex process that occurs in the endoplasmic reticulum (ER) and requires the participation of multiple enzymes. GlcNAc-1-P-transferase (GPT) is essential for initiating N-glycosylation in the ER. Tunicamycin is a natural product that inhibits N-glycosylation and produces ER stress, and thus it is utilized in research. The molecular mechanism by which GPT triggers N-glycosylation is discussed in this review based on the GPT structure. Based on the structure of the GPT-tunicamycin complex, we also discuss how tunicamycin reduces GPT activity, which prevents N-glycosylation. This review will be highly useful for understanding the role of GPT in the N-glycosylation of proteins, as well as presents a potential for considering tunicamycin as an antibiotic treatment.

Automated summary

N-glycosylation is a common post-translational modification that affects protein stability and folding. GlcNAc-1-P-transferase (GPT) plays a crucial role in initiating N-glycosylation in the endoplasmic reticulum (ER). Tunicamycin, a natural product that inhibits N-glycosylation and induces ER stress, is used to investigate the molecular mechanisms of GPT and its inhibition by tunicamycin. This review provides insights into the role of GPT in N-glycosylation and suggests the potential use of tunicamycin as an antibiotic.