8yp3 | pdb_00008yp3

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

spinqualitylabelsall models 8yp3, resolution 2.12Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8yp3 is a 4 chain structure with sequence from Spodoptera frugiperda. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.12Å Ligands: MG, SO4, UD1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A2H1VI03_SPOFR Publication Abstract from PubMed UDP-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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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