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| | <StructureSection load='6dja' size='340' side='right'caption='[[6dja]], [[Resolution|resolution]] 2.48Å' scene=''> | | <StructureSection load='6dja' size='340' side='right'caption='[[6dja]], [[Resolution|resolution]] 2.48Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6dja]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_14579 Atcc 14579]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DJA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DJA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6dja]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_cereus Bacillus cereus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DJA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DJA FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.48Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6dja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dja OCA], [http://pdbe.org/6dja PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dja RCSB], [http://www.ebi.ac.uk/pdbsum/6dja PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dja 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=6dja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dja OCA], [https://pdbe.org/6dja PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dja RCSB], [https://www.ebi.ac.uk/pdbsum/6dja PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dja ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BLAB_BACCE BLAB_BACCE]] Confers resistance to the different beta-lactams antibiotics (penicillin, cephalosporin and carbapenem) via the hydrolysis of the beta-lactam ring. Benzylpenicillin is a better substrate than cephalosporin C and ampicillin (PubMed:3131315, PubMed:2501295).<ref>PMID:1904717</ref> <ref>PMID:2501295</ref> <ref>PMID:3131315</ref> | + | [https://www.uniprot.org/uniprot/BLAB_BACCE BLAB_BACCE] Confers resistance to the different beta-lactams antibiotics (penicillin, cephalosporin and carbapenem) via the hydrolysis of the beta-lactam ring. Benzylpenicillin is a better substrate than cephalosporin C and ampicillin (PubMed:3131315, PubMed:2501295).<ref>PMID:1904717</ref> <ref>PMID:2501295</ref> <ref>PMID:3131315</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6dja" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6dja" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 14579]] | + | [[Category: Bacillus cereus]] |
| - | [[Category: Beta-lactamase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bui, A A]] | + | [[Category: Bui AA]] |
| - | [[Category: Khan, N H]] | + | [[Category: Khan NH]] |
| - | [[Category: Shaw, R W]] | + | [[Category: Shaw RW]] |
| - | [[Category: Sutton, R B]] | + | [[Category: Sutton RB]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Lactamase]]
| + | |
| - | [[Category: Zinc]]
| + | |
| Structural highlights
Function
BLAB_BACCE Confers resistance to the different beta-lactams antibiotics (penicillin, cephalosporin and carbapenem) via the hydrolysis of the beta-lactam ring. Benzylpenicillin is a better substrate than cephalosporin C and ampicillin (PubMed:3131315, PubMed:2501295).[1] [2] [3]
Publication Abstract from PubMed
The hydrolysis of beta-lactam antibiotics by beta-lactamase enzymes is the most prominent antibiotic resistance mechanism for many pathogenic bacteria. Out of this broad class of enzymes, metallo-beta-lactamases are of special clinical interest because of their broad substrate specificities. Several in vitro inhibitors for various metallo-beta-lactamases have been reported with no clinical efficacy. Previously, we described a 10-nucleotide single stranded DNA aptamer (10-mer) that inhibits Bacillus cereus 5/B/6 metallo-beta-lactamase very effectively. Here, we find that the aptamer shows uncompetitive inhibition of Bacillus cereus 5/B/6 metallo-beta-lactamase during cefuroxime hydrolysis. To understand the mechanism of inhibition, we report a 2.5 A resolution X-ray crystal structure and solution-state NMR analysis of the free enzyme. Chemical shift perturbations were observed in the HSQC spectra for several residues upon titrating with increasing concentrations of the 10-mer. In the X-ray crystal structure, these residues are distal to the active site, suggesting an allosteric mechanism for the aptamer inhibition of the enzyme. HADDOCK molecular docking simulations suggest that the 10-mer docks 26 A from the active site. We then mutated the three lysine residues in the basic binding patch to glutamine and measured the catalytic activity and inhibition by the 10-mer. No significant inhibition of these mutants was observed by the 10-mer as compared to wild type. Interestingly, mutation of Lys50 (Lys78; according to standard MBL numbering system) resulted in reduced enzymatic activity relative to wild type in the absence of inhibitor, further highlighting an allosteric mechanism for inhibition.
A DNA aptamer reveals an allosteric site for inhibition in metallo-beta-lactamases.,Khan NH, Bui AA, Xiao Y, Sutton RB, Shaw RW, Wylie BJ, Latham MP PLoS One. 2019 Apr 22;14(4):e0214440. doi: 10.1371/journal.pone.0214440., eCollection 2019. PMID:31009467[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lim HM, Iyer RK, Pene JJ. Site-directed mutagenesis of dicarboxylic acids near the active site of Bacillus cereus 5/B/6 beta-lactamase II. Biochem J. 1991 Jun 1;276 ( Pt 2):401-4. PMID:1904717
- ↑ Lim HM, Pene JJ. Mutations affecting the catalytic activity of Bacillus cereus 5/B/6 beta-lactamase II. J Biol Chem. 1989 Jul 15;264(20):11682-7. PMID:2501295
- ↑ Lim HM, Pene JJ, Shaw RW. Cloning, nucleotide sequence, and expression of the Bacillus cereus 5/B/6 beta-lactamase II structural gene. J Bacteriol. 1988 Jun;170(6):2873-8. doi: 10.1128/jb.170.6.2873-2878.1988. PMID:3131315 doi:http://dx.doi.org/10.1128/jb.170.6.2873-2878.1988
- ↑ Khan NH, Bui AA, Xiao Y, Sutton RB, Shaw RW, Wylie BJ, Latham MP. A DNA aptamer reveals an allosteric site for inhibition in metallo-beta-lactamases. PLoS One. 2019 Apr 22;14(4):e0214440. doi: 10.1371/journal.pone.0214440., eCollection 2019. PMID:31009467 doi:http://dx.doi.org/10.1371/journal.pone.0214440
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