Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Structure-Based Insight on the Mechanism of N-Glycosylation Inhibition by Tunicamycin

  • Danbi Yoon (College of Pharmacy, Chung-Ang University) ;
  • Ju Heun Moon (College of Pharmacy, Chung-Ang University) ;
  • Anna Cho (College of Pharmacy, Chung-Ang University) ;
  • Hyejoon Boo (College of Pharmacy, Chung-Ang University) ;
  • Jeong Seok Cha (College of Pharmacy, Chung-Ang University) ;
  • Yoonji Lee (College of Pharmacy, Chung-Ang University) ;
  • Jiho Yoo (College of Pharmacy, Chung-Ang University)
  • Received : 2023.01.01
  • Accepted : 2023.02.20
  • Published : 2023.06.30
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Abstract

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.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2021R1C1C1012076 to J.Y.) and by the ChungAng University Research Grants in 2020 (to Y.L.).

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