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| | <StructureSection load='3rxx' size='340' side='right'caption='[[3rxx]], [[Resolution|resolution]] 1.62Å' scene=''> | | <StructureSection load='3rxx' size='340' side='right'caption='[[3rxx]], [[Resolution|resolution]] 1.62Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3rxx]] is a 1 chain structure with sequence from [https://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=3RXX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RXX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3rxx]] 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=3RXX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RXX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NPB:3-NITROPHENYLBORONIC+ACID'>NPB</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]] 1.62Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3qxw|3qxw]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NPB:3-NITROPHENYLBORONIC+ACID'>NPB</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">bla, BLAKPC-2, kpc, kpc1 ([https://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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </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=3rxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rxx OCA], [https://pdbe.org/3rxx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rxx RCSB], [https://www.ebi.ac.uk/pdbsum/3rxx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rxx 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=3rxx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rxx OCA], [https://pdbe.org/3rxx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rxx RCSB], [https://www.ebi.ac.uk/pdbsum/3rxx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rxx ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://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;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Class A carbapenemases are a major threat to the potency of carbapenem antibiotics. A widespread carbapenemase, KPC-2, is not easily inhibited by beta-lactamase inhibitors (i.e., clavulanic acid, sulbactam, and tazobactam). To discover different mechanisms of inhibition of KPC-2, we determined the crystal structures of KPC-2 with two beta-lactamase inhibitors that possess different inactivation mechanisms and kinetics. The first complex is of a small boronic acid compound, 3-nitrophenyl boronic acid (3-NPBA) bound to KPC-2 determined at 1.62 A resolution. 3-NPBA demonstrates a K(m) value of 1.0 +/- 0.1 muM for KPC-2 and blocks the active site by making a reversible covalent interaction with the catalytic S70 residue. The two boron hydroxyl atoms of 3-NPBA are positioned in the oxyanion hole and the deacylation water pocket, respectively. In addition, the aromatic ring of 3-NPBA makes an edge-to-face interaction with W105 in the active site. The structure of KPC-2 with the penam sulfone, PSR-3-226, was determined at 1.26 A resolution. PSR-3-226 displays a K(m) value of 3.8 +/- 0.4 muM for KPC-2 and the k(inact) is 0.034 +/- 0.003 s(-1). Covalently bound to S70, PSR-3-226 forms a trans-enamine intermediate in the KPC-2 active site. The predominant active site interactions are generated via the carbonyl oxygen, which resides in the oxyanion hole, and the carboxyl moiety of PSR-3-226 which interacts with N132, N170, and E166. 3-NPBA and PSR-3-226 are the first beta-lactamase inhibitors to be trapped as an acyl-enzyme complex with KPC-2. The structural and inhibitory insights gained herein could aid in the design of potent KPC-2 inhibitors.
| + | |
| - | | + | |
| - | Crystal Structures of KPC-2 beta-Lactamase in Complex with 3-NPBA and PSR-3-226.,Ke W, Bethel CR, Papp-Wallace KM, Pagadala SR, Nottingham M, Fernandez D, Buynak JD, Bonomo RA, van den Akker F Antimicrob Agents Chemother. 2012 Feb 13. PMID:22330909<ref>PMID:22330909</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3rxx" style="background-color:#fffaf0;"></div>
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] |
| - | == References == | |
| - | <references/> | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Beta-lactamase]] | + | [[Category: Klebsiella pneumoniae]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Akker, F van den]]
| + | [[Category: Ke W]] |
| - | [[Category: Ke, W]] | + | [[Category: Van den Akker F]] |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]] | + | |
| - | [[Category: Inhibitor]]
| + | |
