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| | ==Structure of penicillin-binding protein 5 from E.coli: cefoxitin acyl-enzyme complex== | | ==Structure of penicillin-binding protein 5 from E.coli: cefoxitin acyl-enzyme complex== |
| - | <StructureSection load='3mze' size='340' side='right' caption='[[3mze]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='3mze' size='340' side='right'caption='[[3mze]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3mze]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MZE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MZE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3mze]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MZE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MZE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CFX:CEFOXITIN'>CFX</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]] 2.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1nzo|1nzo]], [[1z6f|1z6f]], [[3beb|3beb]], [[3bec|3bec]], [[3mzd|3mzd]], [[3mzf|3mzf]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1QL:(2R)-5-(aminocarbonyloxymethyl)-2-[(1S)-1-methoxy-2-oxidanylidene-1-(2-thiophen-2-ylethanoylamino)ethyl]-3,6-dihydro-2H-1,3-thiazine-4-carboxylic+acid'>1QL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">b0632, dacA, JW0627, pfv ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])</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=3mze FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mze OCA], [https://pdbe.org/3mze PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mze RCSB], [https://www.ebi.ac.uk/pdbsum/3mze PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mze 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=3mze FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mze OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3mze RCSB], [http://www.ebi.ac.uk/pdbsum/3mze PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DACA_ECOLI DACA_ECOLI]] Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors. | + | [https://www.uniprot.org/uniprot/DACA_ECOLI DACA_ECOLI] Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3mze" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Penicillin-binding protein|Penicillin-binding protein]] | + | *[[Penicillin-binding protein 3D structures|Penicillin-binding protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Escherichia coli]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Davies, C]] | + | [[Category: Large Structures]] |
| - | [[Category: Nicholas, R A]] | + | [[Category: Davies C]] |
| - | [[Category: Nicola, G]] | + | [[Category: Nicholas RA]] |
| - | [[Category: Pratt, R F]] | + | [[Category: Nicola G]] |
| - | [[Category: Tomberg, J]] | + | [[Category: Pratt RF]] |
| - | [[Category: Beta-lactam antibiotic]]
| + | [[Category: Tomberg J]] |
| - | [[Category: Dd-carboxypeptidase]]
| + | |
| - | [[Category: Hydrolase]]
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| - | [[Category: Hydrolase-antibiotic complex]]
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| - | [[Category: Penicillin-binding protein]]
| + | |
| Structural highlights
Function
DACA_ECOLI Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors.
Publication Abstract from PubMed
Penicillin-binding proteins (PBPs) are the molecular targets for the widely used beta-lactam class of antibiotics, but how these compounds act at the molecular level is not fully understood. We have determined crystal structures of Escherichia coli PBP 5 as covalent complexes with imipenem, cloxacillin, and cefoxitin. These antibiotics exhibit very different second-order rates of acylation for the enzyme. In all three structures, there is excellent electron density for the central portion of the beta-lactam, but weak or absent density for the R1 or R2 side chains. Areas of contact between the antibiotics and PBP 5 do not correlate with the rates of acylation. The same is true for conformational changes, because although a shift of a loop leading to an electrostatic interaction between Arg248 and the beta-lactam carboxylate, which occurs completely with cefoxitin and partially with imipenem and is absent with cloxacillin, is consistent with the different rates of acylation, mutagenesis of Arg248 decreased the level of cefoxitin acylation only 2-fold. Together, these data suggest that structures of postcovalent complexes of PBP 5 are unlikely to be useful vehicles for the design of new covalent inhibitors of PBPs. Finally, superimposition of the imipenem-acylated complex with PBP 5 in complex with a boronic acid peptidomimetic shows that the position corresponding to the hydrolytic water molecule is occluded by the ring nitrogen of the beta-lactam. Because the ring nitrogen occupies a similar position in all three complexes, this supports the hypothesis that deacylation is blocked by the continued presence of the leaving group after opening of the beta-lactam ring.
Crystal structures of covalent complexes of beta-lactam antibiotics with Escherichia coli penicillin-binding protein 5: toward an understanding of antibiotic specificity.,Nicola G, Tomberg J, Pratt RF, Nicholas RA, Davies C Biochemistry. 2010 Sep 21;49(37):8094-104. PMID:20726582[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nicola G, Tomberg J, Pratt RF, Nicholas RA, Davies C. Crystal structures of covalent complexes of beta-lactam antibiotics with Escherichia coli penicillin-binding protein 5: toward an understanding of antibiotic specificity. Biochemistry. 2010 Sep 21;49(37):8094-104. PMID:20726582 doi:10.1021/bi100879m
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