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| | <StructureSection load='5xp9' size='340' side='right'caption='[[5xp9]], [[Resolution|resolution]] 1.55Å' scene=''> | | <StructureSection load='5xp9' size='340' side='right'caption='[[5xp9]], [[Resolution|resolution]] 1.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5xp9]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XP9 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5XP9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5xp9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XP9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XP9 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BS3:BISMUTH(III)+ION'>BS3</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]] 1.55Å</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=BS3:BISMUTH(III)+ION'>BS3</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5xp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xp9 OCA], [http://pdbe.org/5xp9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xp9 RCSB], [http://www.ebi.ac.uk/pdbsum/5xp9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xp9 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=5xp9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xp9 OCA], [https://pdbe.org/5xp9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xp9 RCSB], [https://www.ebi.ac.uk/pdbsum/5xp9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xp9 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BLAN1_KLEPN BLAN1_KLEPN]] Confers resistance to many beta-lactam antibiotics, including some carbapenems. Does not confer resistance to the polymixin colistin or the fluoroquinolone ciprofloxacin. | + | [https://www.uniprot.org/uniprot/BLAN1_KLEPN BLAN1_KLEPN] Confers resistance to many beta-lactam antibiotics, including some carbapenems. Does not confer resistance to the polymixin colistin or the fluoroquinolone ciprofloxacin. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Beta-lactamase]] | + | [[Category: Klebsiella pneumoniae]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lai, T P]] | + | [[Category: Lai TP]] |
| - | [[Category: Ma, G]] | + | [[Category: Ma G]] |
| - | [[Category: Sun, H]] | + | [[Category: Sun H]] |
| - | [[Category: Zhang, H]] | + | [[Category: Zhang H]] |
| - | [[Category: Antibiotics resistance]]
| + | |
| - | [[Category: Bismuth]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Metallodrug]]
| + | |
| Structural highlights
Function
BLAN1_KLEPN Confers resistance to many beta-lactam antibiotics, including some carbapenems. Does not confer resistance to the polymixin colistin or the fluoroquinolone ciprofloxacin.
Publication Abstract from PubMed
Drug-resistant superbugs pose a huge threat to human health. Infections by Enterobacteriaceae producing metallo-beta-lactamases (MBLs), e.g., New Delhi metallo-beta-lactamase 1 (NDM-1) are very difficult to treat. Development of effective MBL inhibitors to revive the efficacy of existing antibiotics is highly desirable. However, such inhibitors are not clinically available till now. Here we show that an anti-Helicobacter pylori drug, colloidal bismuth subcitrate (CBS), and related Bi(III) compounds irreversibly inhibit different types of MBLs via the mechanism, with one Bi(III) displacing two Zn(II) ions as revealed by X-ray crystallography, leading to the release of Zn(II) cofactors. CBS restores meropenem (MER) efficacy against MBL-positive bacteria in vitro, and in mice infection model, importantly, also slows down the development of higher-level resistance in NDM-1-positive bacteria. This study demonstrates a high potential of Bi(III) compounds as the first broad-spectrum B1 MBL inhibitors to treat MBL-positive bacterial infection in conjunction with existing carbapenems.
Bismuth antimicrobial drugs serve as broad-spectrum metallo-beta-lactamase inhibitors.,Wang R, Lai TP, Gao P, Zhang H, Ho PL, Woo PC, Ma G, Kao RY, Li H, Sun H Nat Commun. 2018 Jan 30;9(1):439. doi: 10.1038/s41467-018-02828-6. PMID:29382822[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wang R, Lai TP, Gao P, Zhang H, Ho PL, Woo PC, Ma G, Kao RY, Li H, Sun H. Bismuth antimicrobial drugs serve as broad-spectrum metallo-beta-lactamase inhibitors. Nat Commun. 2018 Jan 30;9(1):439. doi: 10.1038/s41467-018-02828-6. PMID:29382822 doi:http://dx.doi.org/10.1038/s41467-018-02828-6
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