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| <StructureSection load='6bsq' size='340' side='right'caption='[[6bsq]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='6bsq' size='340' side='right'caption='[[6bsq]], [[Resolution|resolution]] 1.80Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6bsq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"enterococcus_proteiformis"_thiercelin_and_jouhaud_1903 "enterococcus proteiformis" thiercelin and jouhaud 1903]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BSQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BSQ FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6bsq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_faecalis Enterococcus faecalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BSQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BSQ FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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]] 1.8Å</td></tr> |
| <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6bsr|6bsr]]</td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">pbp4, A6B47_10405 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1351 "Enterococcus proteiformis" Thiercelin and Jouhaud 1903])</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=6bsq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bsq OCA], [https://pdbe.org/6bsq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bsq RCSB], [https://www.ebi.ac.uk/pdbsum/6bsq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bsq ProSAT]</span></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6bsq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bsq OCA], [http://pdbe.org/6bsq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bsq RCSB], [http://www.ebi.ac.uk/pdbsum/6bsq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bsq ProSAT]</span></td></tr> | |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
| | == Function == |
| == Publication Abstract from PubMed == | | [https://www.uniprot.org/uniprot/Q9K3C9_ENTFL Q9K3C9_ENTFL] |
| The final steps of cell-wall biosynthesis in bacteria are carried out by penicillin-binding proteins (PBPs), whose transpeptidase domains form the crosslinks in peptidoglycan chains that define the bacterial cell wall. These enzymes are the targets of beta-lactam antibiotics, as their inhibition reduces the structural integrity of the cell wall. Bacterial resistance to antibiotics is a rapidly growing concern; however, the structural underpinnings of PBP-derived antibiotic resistance are poorly understood. PBP4 and PBP5 are low-affinity, class B transpeptidases that confer antibiotic resistance to Enterococcus faecalis and Enterococcus faecium, respectively. Here, we report the crystal structures of PBP4 (1.8 A) and PBP5 (2.7 A) in their apo and acyl-enzyme complexes with the beta-lactams benzylpenicillin, imipenem and ceftaroline. We found that, although these three beta-lactams adopt geometries similar to those observed in other class B PBP structures, there are small, but significant differences that likely decrease antibiotic efficacy. Further, we also discovered that the N-terminal domain extensions in this class of PBPs undergo large rigid-body rotations without impacting the structure of the catalytic transpeptidase domain. Together, our findings are defining the subtle functional and structural differences in the enterococcus PBPs that allow them to support transpeptidase activity while also conferring bacterial resistance to antibiotics that function as substrate mimics.
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| The structures of penicillin binding protein 4 (PBP4) and PBP5 from Enterococci provide structural insights into beta-lactam resistance.,Moon TM, D'Andrea ED, Lee CW, Soares A, Jakoncic J, Desbonnet C, Solache MG, Rice LB, Page R, Peti W J Biol Chem. 2018 Oct 24. pii: RA118.006052. doi: 10.1074/jbc.RA118.006052. PMID:30355734<ref>PMID:30355734</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 6bsq" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]] | | *[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Enterococcus proteiformis thiercelin and jouhaud 1903]] | | [[Category: Enterococcus faecalis]] |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Andrea, E D.D]] | | [[Category: D'Andrea ED]] |
| [[Category: Moon, T M]] | | [[Category: Moon TM]] |
| [[Category: Page, R]] | | [[Category: Page R]] |
| [[Category: Peti, W]] | | [[Category: Peti W]] |
| [[Category: Antibiotic]]
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| [[Category: Beta-lactam]]
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| [[Category: Hydrolase]]
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| [[Category: Penicillin binding protein]]
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| [[Category: Transpeptidase]]
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