View source for 3rxx


==KPC-2 carbapenemase in complex with 3-NPBA==
<StructureSection load='3rxx' size='340' side='right'caption='[[3rxx]], [[Resolution|resolution]] 1.62&Aring;' scene=''>
== Structural highlights ==
<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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.62&#8491;</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='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>
== Function ==
[https://www.uniprot.org/uniprot/BLKPC_KLEPN BLKPC_KLEPN] Hydrolyzes carbapenems, penicillins, cephalosporins and monobactams with varying efficiency.
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== 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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3rxx" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Klebsiella pneumoniae]]
[[Category: Large Structures]]
[[Category: Ke W]]
[[Category: Van den Akker F]]