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| | <StructureSection load='4zbe' size='340' side='right'caption='[[4zbe]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='4zbe' size='340' side='right'caption='[[4zbe]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4zbe]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_pneumoniae"_(schroeter_1886)_flugge_1886 "bacillus pneumoniae" (schroeter 1886) flugge 1886]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZBE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZBE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4zbe]] 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=4ZBE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZBE FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=NXL:(2S,5R)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>NXL</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">[[4fh4|4fh4]], [[4zam|4zam]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=NXL:(2S,5R)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>NXL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bla, kpc, kpc1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=573 "Bacillus pneumoniae" (Schroeter 1886) Flugge 1886])</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=4zbe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zbe OCA], [https://pdbe.org/4zbe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zbe RCSB], [https://www.ebi.ac.uk/pdbsum/4zbe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zbe ProSAT]</span></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>
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| - | <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=4zbe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zbe OCA], [http://pdbe.org/4zbe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zbe RCSB], [http://www.ebi.ac.uk/pdbsum/4zbe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zbe ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BLKPC_KLEPN BLKPC_KLEPN]] Hydrolyzes carbapenems, penicillins, cephalosporins and monobactams with varying efficiency. | + | [https://www.uniprot.org/uniprot/BLKPC_KLEPN BLKPC_KLEPN] Hydrolyzes carbapenems, penicillins, cephalosporins and monobactams with varying efficiency. |
| | <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: Akker, F van den]]
| + | [[Category: Nguyen NQ]] |
| - | [[Category: Nguyen, N Q]] | + | [[Category: Van den Akker F]] |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]] | + | |
| Structural highlights
Function
BLKPC_KLEPN Hydrolyzes carbapenems, penicillins, cephalosporins and monobactams with varying efficiency.
Publication Abstract from PubMed
beta-Lactamase inhibition is an important clinical strategy in overcoming beta-lactamase-mediated resistance to beta-lactam antibiotics in Gram negative bacteria. A new beta-lactamase inhibitor, avibactam, is entering the clinical arena and promising to be a major step forward in our antibiotic armamentarium. Avibactam has remarkable broad-spectrum activity in being able to inhibit classes A, C, and some class D beta-lactamases. We present here structural investigations into class A beta-lactamase inhibition by avibactam as we report the crystal structures of SHV-1, the chromosomal penicillinase of Klebsiella pneumoniae, and KPC-2, an acquired carbapenemase found in the same pathogen, complexed with avibactam. The 1.80 A KPC-2 and 1.42 A resolution SHV-1 beta-lactamase avibactam complex structures reveal avibactam covalently bonded to the catalytic S70 residue. Analysis of the interactions and chair-shaped conformation of avibactam bound to the active sites of KPC-2 and SHV-1 provides structural insights into recently laboratory-generated amino acid substitutions that result in resistance to avibactam in KPC-2 and SHV-1. Furthermore, we observed several important differences in the interactions with amino acid residues, in particular that avibactam forms hydrogen bonds to S130 in KPC-2 but not in SHV-1, that can possibly explain some of the different kinetic constants of inhibition. Our observations provide a possible reason for the ability of KPC-2 beta-lactamase to slowly desulfate avibactam with a potential role for the stereochemistry around the N1 atom of avibactam and/or the presence of an active site water molecule that could aid in avibactam desulfation, an unexpected consequence of novel inhibition chemistry.
Inhibition of Klebsiella beta-Lactamases (SHV-1 and KPC-2) by Avibactam: A Structural Study.,Krishnan NP, Nguyen NQ, Papp-Wallace KM, Bonomo RA, van den Akker F PLoS One. 2015 Sep 4;10(9):e0136813. doi: 10.1371/journal.pone.0136813., eCollection 2015. PMID:26340563[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Krishnan NP, Nguyen NQ, Papp-Wallace KM, Bonomo RA, van den Akker F. Inhibition of Klebsiella beta-Lactamases (SHV-1 and KPC-2) by Avibactam: A Structural Study. PLoS One. 2015 Sep 4;10(9):e0136813. doi: 10.1371/journal.pone.0136813., eCollection 2015. PMID:26340563 doi:http://dx.doi.org/10.1371/journal.pone.0136813
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