BACKGROUND NXL104 is a novel-structure beta-lactamase inhibitor with potent activity against both class A and class C enzymes. Among the class A carbapenemases, KPC-type enzymes are now spreading rapidly and KPC-related carbapenemase resistance is an emerging phenomenon of great clinical importance. The activity of NXL104 against KPC beta-lactamases was examined. METHODS Enzymatic activity of...

Crystallographic studies of the complex between beta-lactamase and clavulanate reveal a structure of two acyl-enzymes with covalent bonds at the active site Ser70, representing two different stages of inhibitor degradation alternately occupying the active site. Models that are consistent with biochemical data are derived from the electron density map and refined at 2.2 A resolution: cis enamine...

to be developed. -lactamases are the most widespread resistance Several classes of non-lactam inhibitors of -lactamechanisms to -lactam antibiotics, and there is a mases have been identified. Transition-state analog inpressing need for novel, non-lactam drugs. A datahibitors (Figure 1C), such as boronic acids and phosphobase of over 200,000 compounds was docked to the nates, inhibit both class ...

BACKGROUND & OBJECTIVES AmpC beta-lactamases are Group I cephalosporinases that confer resistance to a wide variety of beta-lactam drugs. Plasmid mediated AmpC beta-lactamases has been discovered most frequently in isolates of Klebsiella pneumoniae, K. oxytoca, Salmonella, Proteus mirabilis and Escherichia coli. The present study was undertaken to study the occurrence of multidrug resistant and...

Boronic acids have proved to be promising selective inhibitors of beta-lactamases, acting as transition state analogues. Starting from a previously described nanomolar inhibitor of AmpC beta-lactamase, three new inhibitors were designed to gain interactions with highly conserved residues, such as Asn343, and to bind more tightly to the enzyme. Among these, one was obtained by stereoselective sy...