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The reaction mechanism of a novel methylidene penem, which inhibited a class C [beta]-lactamase GC1 is analyzed. A quantum chemical modeling is used to describe the form of a seven-membered ring complex and tautomerism between intermediates.

Enzyme destabilization by truncation is combined with directed evolution to create stable variants of TEM-1 beta-lactamase. Structural perturbation by terminal truncation, evolutionary compensation at physiological temperatures, and elongation is an efficient way to analyze and improve thermostability without the need for high-temperature selection, structural information, or homologous proteins.

The high-resolution crystal structure of the class D OXA-10 beta-lactamase inhibited by a penicillanate derivative is reported. The structure provides evidence that the varboxylated Lys-70 is intimately involved in the mechanism of the enzyme.

The screening study was conducted to determine the presence of metallo-beta-lactamases (IMP and VIM types and SPM-1) in isolates from different nonhospital sources. The results have indicated that the hospital setting was the possible origin of these [bla.sub.VIM-2]-carrying strains.

Molecular modeling was employed to explore the mechanism underlying the [alpha]-hydroxy group interaction with the class C [beta]-lactamase active site. The [alpha]-hydroxyalkyl moiety with ability to spontaneously decarboxylate in aqueous neutral buffer to form O-(2-hydroxyalkylcarbonyl) hydroxamates might find potential application when incorporated with novel inhibitors.

The K73A and E166A mutant forms of [beta]-lactamase, BlaC were prepared to determine the structures of the Michaelis complex of cefamandole and the covalently bound acyl intermediate of cefamandole at resolutions of 1.2 and 2.0 [Angstrom], respectively. The structures provide insight into the details of the catalytic mechanism associated with active sites of the Mycobacterium tuberculosis [beta]-Lactamase K73A and E166A Mutants which are essential for acylation and deacylation, respectively.

A high-resolution structure of enzyme Co(II)-BcII from Bacillus cereus which revealed a metal coordination geometry identical to that of the native zinc enzyme dependent [beta]-lactamase is presented. A considerable flexibility observed in the two loops of Cys ligand containing four metal ligands could assist in the in the structural rearrangement of the metal sites during catalytic turnover, which, along with the coordination geometry adaptability of Zn(II) ions, grants the interaction with a variety of substrates, a characteristic feature of B1 metallo-[beta[-lactamases.

The interaction between KPC-2 [beta]-lactamase and [beta]-lactamase inhibitor protein (BLIP) is characterized. The continuing emergence of antibiotic resistance has facilitated the high-resolution KPC-2-BLIP structure to be used as a template for the rational design of new inhibitors of this enzyme.