3rxw

KPC-2 carbapenemase in complex with PSR3-226

spinqualitylabelsall models 3rxw, resolution 1.26Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3rxw is a 1 chain structure with sequence from Klebsiella pneumoniae. The July 2015 RCSB PDB Molecule of the Month feature on New Delhi Metallo-b-Lactamase by David Goodsell is 10.2210/rcsb_pdb/mom_2015_7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.26Å Ligands: CIT, SR3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BLKPC_KLEPN Hydrolyzes carbapenems, penicillins, cephalosporins and monobactams with varying efficiency. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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