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==Crystal structure of bifunctional GlmU from Staphylococcus aureus NCTC 8325 complexed with acetyl CoA and citrate==
<StructureSection load='9dqf' size='340' side='right'caption='[[9dqf]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9dqf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_NCTC_8325 Staphylococcus aureus subsp. aureus NCTC 8325]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9DQF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9DQF 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</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=9dqf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9dqf OCA], [https://pdbe.org/9dqf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9dqf RCSB], [https://www.ebi.ac.uk/pdbsum/9dqf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9dqf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GLMU_STAA8 GLMU_STAA8] Catalyzes the last two sequential reactions in the de novo biosynthetic pathway for UDP-N-acetylglucosamine (UDP-GlcNAc). The C-terminal domain catalyzes the transfer of acetyl group from acetyl coenzyme A to glucosamine-1-phosphate (GlcN-1-P) to produce N-acetylglucosamine-1-phosphate (GlcNAc-1-P), which is converted into UDP-GlcNAc by the transfer of uridine 5-monophosphate (from uridine 5-triphosphate), a reaction catalyzed by the N-terminal domain.
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== Publication Abstract from PubMed ==
The bifunctional enzyme N-acetylglucosamine 1-phosphate uridyltransferase (GlmU) is a promising antibiotic drug target, as it facilitates the biosynthesis of uridine 5'-diphospho-N-acetylglucosamine, an essential precursor of cell wall constituents. We identified that Staphylococcus aureus GlmU (SaGlmU), which was previously targeted for inhibitor development, possesses a dual-cysteine variation (C379/C404) within the acetyltransferase active site. Enzyme assays performed under reducing and non-reducing conditions revealed that the acetyltransferase activity of SaGlmU is redox-sensitive, displaying ~15-fold lower turnover and ~3-fold higher K(M) value for the acetyl CoA substrate under non-reducing conditions. This sensitivity was absent in a C379A SaGlmU mutant. Analysis of SaGlmU by mass spectrometry, x-ray crystallography, and in silico modeling support that C379 and C404 act as a reversible, redox-sensitive switch by forming a disulfide under non-reducing conditions that impedes acetyl CoA recognition and turnover. Therefore, we recommend that future in vitro screening and characterization of SaGlmU inhibitors consider both reducing and non-reducing conditions.

Functional and structural characterization of Staphylococcus aureus N-acetylglucosamine 1-phosphate uridyltransferase (GlmU) reveals a redox-sensitive acetyltransferase activity.,Pederick JL, Kumar A, Pukala TL, Bruning JB Protein Sci. 2025 Apr;34(4):e70111. doi: 10.1002/pro.70111. PMID:40143772<ref>PMID:40143772</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Staphylococcus aureus subsp. aureus NCTC 8325]]
[[Category: Bruning JB]]
[[Category: Pederick JL]]