8YP3

Crystal structure of UDP-N-acetylglucosamine pyrophosphorylase from Spodoptera frugiperda in complex with UDP-GlcNAc

Summary for 8YP3

• Entry DOI: 10.2210/pdb8yp3/pdb
• Descriptor: UDP-N-acetylglucosamine diphosphorylase, URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE, SULFATE ION, ... (5 entities in total)
• Functional Keywords: udp-n-acetylglucosamine pyrophosphorylase, spodoptera frugiperda, udp-glcnac, sugar binding protein
• Biological source: Spodoptera frugiperda (fall armyworm)
• Total number of polymer chains: 4
• Total formula weight: 220832.15

Authors

Lu, Q.,Liu, T.,Zhou, Y.,Yang, Q. (deposition date: 2024-03-15, release date: 2024-08-07, Last modification date: 2024-09-18)

Primary citation

Lu, Q.,Zhou, Y.,Ding, Y.,Cui, Y.,Li, W.,Liu, T.
Structure and Inhibition of Insect UDP- N -acetylglucosamine Pyrophosphorylase: A Key Enzyme in the Hexosamine Biosynthesis Pathway.
J.Agric.Food Chem., 72:19286-19294, 2024

PubMed Abstract: UDP--acetylglucosamine pyrophosphorylase (UAP) catalyzes the last step in the hexosamine biosynthesis pathway to directly produce UDP--acetylglucosamine (UDP-GlcNAc). Because UAPs play important physiological and pathological roles in organisms, they are considered potential targets for drug and pesticide development. However, the lack of efficient and selective inhibitors is a bottleneck that must be overcome. This study reports the first crystal structure of the insect UAP from (UAP) in complex with UDP-GlcNAc. UAP has two insect-specific structural characteristics in the active pocket, namely, a free Cys (Cys) and a Mg binding site, which differentiate it from human UAP (AGX1) and fungal UAP (UAP) in terms of substrate and inhibitor binding. -(4-Nitrophenyl)maleimide (NPMI) and myricetin are discovered as potent covalent and noncovalent inhibitors of UAP, respectively. Moreover, myricetin can significantly reduce the level of cellular -GlcNAcylation by inhibiting both UAP and -GlcNAc transferase. These findings provide novel insights into the development of UAP-based drugs and pesticides.

PubMed: 39039661
DOI: 10.1021/acs.jafc.4c03834

Experimental method

X-RAY DIFFRACTION (2.12 Å)