7kcx

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Current revision (11:05, 23 October 2024) (edit) (undo)
 
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<StructureSection load='7kcx' size='340' side='right'caption='[[7kcx]], [[Resolution|resolution]] 1.62&Aring;' scene=''>
<StructureSection load='7kcx' size='340' side='right'caption='[[7kcx]], [[Resolution|resolution]] 1.62&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[7kcx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_COL Staphylococcus aureus subsp. aureus COL]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KCX FirstGlance]. <br>
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KCX 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]] 1.62&#8491;</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.62&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1S7:(2R)-2-{(1S)-1-METHOXY-2-OXO-1-[(THIOPHEN-2-YLACETYL)AMINO]ETHYL}-5-METHYLIDENE-5,6-DIHYDRO-2H-1,3-THIAZINE-4-CARBOXYLIC+ACID'>1S7</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1S7:(2R)-2-{(1S)-1-METHOXY-2-OXO-1-[(THIOPHEN-2-YLACETYL)AMINO]ETHYL}-5-METHYLIDENE-5,6-DIHYDRO-2H-1,3-THIAZINE-4-CARBOXYLIC+ACID'>1S7</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=7kcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kcx OCA], [https://pdbe.org/7kcx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kcx RCSB], [https://www.ebi.ac.uk/pdbsum/7kcx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kcx ProSAT]</span></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=7kcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kcx OCA], [https://pdbe.org/7kcx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kcx RCSB], [https://www.ebi.ac.uk/pdbsum/7kcx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kcx ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
 
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[https://www.uniprot.org/uniprot/A0A0H2WY27_STAAC A0A0H2WY27_STAAC]
 
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<div style="background-color:#fffaf0;">
 
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== Publication Abstract from PubMed ==
 
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BACKGROUND: PBP4, a low-molecular-weight PBP in Staphylococcus aureus, is not considered to be a classical mediator of beta-lactam resistance. Previous studies carried out by our group with laboratory strains of S. aureus demonstrated the ability of PBP4 to produce beta-lactam resistance through mutations associated with the pbp4 promoter and/or gene. Recent studies of beta-lactam-resistant clinical isolates of S. aureus have reported similar mutations associated with pbp4. OBJECTIVES: To determine if pbp4-associated mutations reported among clinical strains of S. aureus mediate beta-lactam resistance. METHODS: The pbp4 promoters and genes bearing mutations from clinical isolates were cloned into a heterologous host. Reporter, growth and Bocillin assays were performed to assess their role in beta-lactam resistance. X-ray crystallography was used to obtain acyl-enzyme intermediate structures of the WT and mutant PBP4 with nafcillin and cefoxitin. RESULTS: Of the five strains that contained pbp4 promoter mutations, three strains exhibited enhanced expression of PBP4. The R200L mutation in pbp4 resulted in increased survival in the presence of the beta-lactams nafcillin and cefoxitin. Further, introduction of either a promoter or a gene mutation into the genome of a WT host increased the ability of the strains to resist the action of beta-lactams. The four high-resolution X-ray structures presented demonstrate the binding pose of the beta-lactams tested and provide hints for further drug development. CONCLUSIONS: Mutations associated with the pbp4 promoter and pbp4 gene altered protein activity and mediated beta-lactam resistance among the clinically isolated strains that were studied.
 
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PBP4-mediated beta-lactam resistance among clinical strains of Staphylococcus aureus.,Satishkumar N, Alexander JAN, Poon R, Buggeln E, Argudin MA, Strynadka NCJ, Chatterjee SS J Antimicrob Chemother. 2021 Jun 21. pii: 6307153. doi: 10.1093/jac/dkab201. PMID:34151961<ref>PMID:34151961</ref>
 
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
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</div>
 
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<div class="pdbe-citations 7kcx" style="background-color:#fffaf0;"></div>
 
==See Also==
==See Also==
*[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]]
*[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]]
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== References ==
 
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<references/>
 
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Staphylococcus aureus subsp. aureus COL]]
 
[[Category: Alexander JAN]]
[[Category: Alexander JAN]]
[[Category: Strynadka NCJ]]
[[Category: Strynadka NCJ]]

Current revision

Crystal structure of S. aureus penicillin-binding protein 4 (PBP4) mutant (R200L) in complex with cefoxitin

PDB ID 7kcx

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