8yp3
Crystal structure of UDP-N-acetylglucosamine pyrophosphorylase from Spodoptera frugiperda in complex with UDP-GlcNAcCrystal structure of UDP-N-acetylglucosamine pyrophosphorylase from Spodoptera frugiperda in complex with UDP-GlcNAc
Structural highlights
FunctionPublication Abstract from PubMedUDP-N-acetylglucosamine pyrophosphorylase (UAP) catalyzes the last step in the hexosamine biosynthesis pathway to directly produce UDP-N-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 Spodoptera frugiperda (SfUAP) in complex with UDP-GlcNAc. SfUAP has two insect-specific structural characteristics in the active pocket, namely, a free Cys (Cys(334)) and a Mg(2+) binding site, which differentiate it from human UAP (HsAGX1) and fungal UAP (AfUAP) in terms of substrate and inhibitor binding. N-(4-Nitrophenyl)maleimide (pNPMI) and myricetin are discovered as potent covalent and noncovalent inhibitors of SfUAP, respectively. Moreover, myricetin can significantly reduce the level of cellular O-GlcNAcylation by inhibiting both UAP and O-GlcNAc transferase. These findings provide novel insights into the development of UAP-based drugs and pesticides. Structure and Inhibition of Insect UDP-N-acetylglucosamine Pyrophosphorylase: A Key Enzyme in the Hexosamine Biosynthesis Pathway.,Lu Q, Zhou Y, Ding Y, Cui Y, Li W, Liu T J Agric Food Chem. 2024 Jul 22. doi: 10.1021/acs.jafc.4c03834. PMID:39039661[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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