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7kcy
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 7kcy is ON HOLD Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of S. aureus penicillin-binding protein 4 (PBP4) with cefoxitin== | |
| + | <StructureSection load='7kcy' size='340' side='right'caption='[[7kcy]], [[Resolution|resolution]] 1.85Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7kcy]] 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=7KCY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KCY 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=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=7kcy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kcy OCA], [https://pdbe.org/7kcy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kcy RCSB], [https://www.ebi.ac.uk/pdbsum/7kcy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kcy ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/A0A0H2WY27_STAAC A0A0H2WY27_STAAC] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| - | + | 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> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7kcy" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Staphylococcus aureus subsp. aureus COL]] | ||
| + | [[Category: Alexander JAN]] | ||
| + | [[Category: Strynadka NCJ]] | ||
Current revision
Crystal structure of S. aureus penicillin-binding protein 4 (PBP4) with cefoxitin
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