4gzb | pdb_00004gzb

Crystal structure of native AmpC beta-lactamase from Pseudomonas aeruginosa PAO1

spinqualitylabelsall models 4gzb, resolution 1.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4gzb is a 1 chain structure with sequence from Pseae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO Related: 4hbt, 4hbu, 4hef Gene: ampC, blaAmpC, PA4110 (PSEAE) Activity: Beta-lactamase, with EC number 3.5.2.6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Although beta-lactams have been the most effective class of antibacterial agents used in clinical practice for the past half century, their effectiveness on Gram-negative bacteria has been eroded due to the emergence and spread of beta-lactamase enzymes that are not affected by currently marketed beta-lactam/beta-lactamase inhibitor combinations. Avibactam is a novel, covalent, non-beta-lactam beta-lactamase inhibitor presently in clinical development in combination with either ceftaroline or ceftazidime. In vitro studies show that avibactam may restore the broad-spectrum activity of cephalosporins against class A, class C and some class D beta-lactamases. Here we describe the structure of two clinically important beta-lactamase enzymes bound to avibactam, the class A CTX-M-15 extended-spectrum beta-lactamase and class C Pseudomonas aeruginosa AmpC beta-lactamase, which together provide insight into the binding modes for the respective enzyme classes. The structure reveals a similar binding mode in both enzymes and thus provides a rationale for the broad-spectrum inhibitory activity of avibactam. Identification of the key residues surrounding the binding pocket allows for a better understanding of the potency of this scaffold. Finally, avibactam has recently been shown to be a reversible inhibitor and the structure provides insights into the mechanism of avibactam recyclization. Analysis of the ultra-high resolution CTX-M-15 structure suggests how the deacylation mechanism favors recyclization over hydrolysis. Structural Insight into Potent Broad-spectrum Inhibition with Reversible Recyclization Mechanism: Avibactam in Complex with CTX-M-15 and Pseudomonas aeruginosa AmpC beta-lactamases.,Lahiri SD, Mangani S, Durand-Reville T, Benvenuti M, De Luca F, Sanyal G, Docquier JD Antimicrob Agents Chemother. 2013 Feb 25. PMID:23439634 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase

Proteopedia Page Contributors and Editors (what is this?)

OCA