4zbe

Crystal structure of KPC-2 beta-lactamase complexed with avibactam

spinqualitylabelsall models 4zbe, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4zbe is a 1 chain structure with sequence from Klebsiella pneumoniae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: CIT, NXL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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