View source for 7kr9


==Bifunctional enzyme GlmU bound to Zn(II)==
<StructureSection load='7kr9' size='340' side='right'caption='[[7kr9]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7kr9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_D39 Streptococcus pneumoniae D39]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KR9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KR9 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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7kr9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kr9 OCA], [https://pdbe.org/7kr9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kr9 RCSB], [https://www.ebi.ac.uk/pdbsum/7kr9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kr9 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GLMU_STRP2 GLMU_STRP2] 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 ==
Streptococcus pneumoniae is the primary cause of community-acquired bacterial pneumonia with rates of penicillin and multidrug-resistance exceeding 80% and 40%, respectively. The innate immune response generates a variety of antimicrobial agents to control infection, including zinc stress. Here, we characterize the impact of zinc intoxication on S. pneumoniae, observing disruptions in central carbon metabolism, lipid biogenesis, and peptidoglycan biosynthesis. Characterization of the pivotal peptidoglycan biosynthetic enzyme GlmU indicates a sensitivity to zinc inhibition. Disruption of the sole zinc efflux pathway, czcD, renders S. pneumoniae highly susceptible to beta-lactam antibiotics. To dysregulate zinc homeostasis in the wild-type strain, we investigated the safe-for-human-use ionophore 5,7-dichloro-2-[(dimethylamino)methyl]quinolin-8-ol (PBT2). PBT2 rendered wild-type S. pneumoniae strains sensitive to a range of antibiotics. Using an invasive ampicillin-resistant strain, we demonstrate in a murine pneumonia infection model the efficacy of PBT2 + ampicillin treatment. These findings present a therapeutic modality to break antibiotic resistance in multidrug-resistant S. pneumoniae.

Dysregulation of Streptococcus pneumoniae zinc homeostasis breaks ampicillin resistance in a pneumonia infection model.,Brazel EB, Tan A, Neville SL, Iverson AR, Udagedara SR, Cunningham BA, Sikanyika M, De Oliveira DMP, Keller B, Bohlmann L, El-Deeb IM, Ganio K, Eijkelkamp BA, McEwan AG, von Itzstein M, Maher MJ, Walker MJ, Rosch JW, McDevitt CA Cell Rep. 2022 Jan 11;38(2):110202. doi: 10.1016/j.celrep.2021.110202. PMID:35021083<ref>PMID:35021083</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7kr9" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Streptococcus pneumoniae D39]]
[[Category: Maher MJ]]