8WVD

Crystal structure of Glycosyltransferase in complex with UD1

8WVD の概要

• エントリーDOI: 10.2210/pdb8wvd/pdb
• 分子名称: Glycosyltransferase, URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE (3 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: Siraitia grosvenorii
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 51828.83

構造登録者

Li, J.,Shan, N.,Yang, J.G.,Liu, W.D.,Sun, Y.X. (登録日: 2023-10-23, 公開日: 2024-09-04, 最終更新日: 2024-10-23)

主引用文献

Li, J.,Li, R.,Shang, N.,Men, Y.,Cai, Y.,Zeng, Y.,Liu, W.,Yang, J.,Sun, Y.
Enzymatic Synthesis of Novel Terpenoid Glycoside Derivatives Decorated with N -Acetylglucosamine Catalyzed by UGT74AC1.
J.Agric.Food Chem., 72:14255-14263, 2024

PubMed Abstract: The addition of the -linked -acetylglucosamine (-GlcNAc) is a significant modification for active molecules, such as proteins, carbohydrates, and natural products. However, the synthesis of terpenoid glycoside derivatives decorated with GlcNAc remains a challenging task due to the absence of glycosyltransferases, key enzymes for catalyzing the transfer of GlcNAc to terpenoids. In this study, we demonstrated that the enzyme mutant UGT74AC1 efficiently transferred GlcNAc from uridine diphosphate (UDP)-GlcNAc to a variety of terpenoids. This powerful enzyme was employed to synthesize GlcNAc-decorated derivatives of terpenoids, including mogrol, steviol, andrographolide, protopanaxadiol, glycyrrhetinic acid, ursolic acid, and betulinic acid for the first time. To unravel the mechanism of UDP-GlcNAc recognition, we determined the X-ray crystal structure of the inactivated mutant UGT74AC1 in complex with UDP-GlcNAc at a resolution of 1.66 Å. Through molecular dynamic simulation and activity analysis, we revealed the molecular mechanism and catalytically important amino acids directly involved in the recognition of UDP-GlcNAc. Overall, this study not only provided a potent biocatalyst capable of glycodiversifying natural products but also elucidated the structural basis for UDP-GlcNAc recognition by glycosyltransferases.

PubMed: 38867497
DOI: 10.1021/acs.jafc.4c02832

実験手法

X-RAY DIFFRACTION (1.66 Å)