9dr4
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 9dr4 is ON HOLD Authors: Description: Category: Unreleased Structures) |
|||
| (2 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of bifunctional GlmU from Staphylococcus aureus NCTC 8325 complexed with UTP, CoA and Glc 1-P== | |
| + | <StructureSection load='9dr4' size='340' side='right'caption='[[9dr4]], [[Resolution|resolution]] 1.85Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9dr4]] 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=9DR4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9DR4 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]] 1.85Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=G1P:ALPHA-D-GLUCOSE-1-PHOSPHATE'>G1P</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=UTP:URIDINE+5-TRIPHOSPHATE'>UTP</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=9dr4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9dr4 OCA], [https://pdbe.org/9dr4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9dr4 RCSB], [https://www.ebi.ac.uk/pdbsum/9dr4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9dr4 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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 9dr4" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Staphylococcus aureus subsp. aureus NCTC 8325]] | ||
| + | [[Category: Bruning JB]] | ||
| + | [[Category: Pederick JL]] | ||
Current revision
Crystal structure of bifunctional GlmU from Staphylococcus aureus NCTC 8325 complexed with UTP, CoA and Glc 1-P
| |||||||||||
