View source for 8yp3


==Crystal structure of UDP-N-acetylglucosamine pyrophosphorylase from Spodoptera frugiperda in complex with UDP-GlcNAc==
<StructureSection load='8yp3' size='340' side='right'caption='[[8yp3]], [[Resolution|resolution]] 2.12&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8yp3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Spodoptera_frugiperda Spodoptera frugiperda]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8YP3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8YP3 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.12&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UD1:URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE'>UD1</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8yp3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8yp3 OCA], [https://pdbe.org/8yp3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8yp3 RCSB], [https://www.ebi.ac.uk/pdbsum/8yp3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8yp3 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A2H1VI03_SPOFR A0A2H1VI03_SPOFR] 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:39039661</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8yp3" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Spodoptera frugiperda]]
[[Category: Liu T]]
[[Category: Lu Q]]
[[Category: Yang Q]]
[[Category: Zhou Y]]