8WVD

Crystal structure of Glycosyltransferase in complex with UD1

Summary for 8WVD

• Entry DOI: 10.2210/pdb8wvd/pdb
• Descriptor: Glycosyltransferase, URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE (3 entities in total)
• Functional Keywords: transferase
• Biological source: Siraitia grosvenorii
• Total number of polymer chains: 1
• Total formula weight: 51828.83

Authors

Li, J.,Shan, N.,Yang, J.G.,Liu, W.D.,Sun, Y.X. (deposition date: 2023-10-23, release date: 2024-09-04, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.66 Å)