X-Ray Structure of the Complex with a Bridged Monobactam

The stability of the acyl-enzyme complexes formed with C freundii class C beta-lactamase allowed solution of their structures by X-ray crystallography (Fig. 8). No significant changes in protein structure occurred, except that the side chain of Aspl23 moved to accommodate 

5 Structure-Based Design of Potent Beta-Lactamase Inhibitors 

A rotation about the amide bond of the acyl side chain by approximately 35°, compared to the aztreonam complex, is observed in the inhibitor complexes. This different vector is imposed by the pyrrolidine ring. It has the consequence of placing the side chain deeper in the active site. In turn, this restricts the options for side chain variation to compounds that have small substituents in the alpha-position and that are relatively flexible. Rigid side chains such as that of aztreonam are not compatible with these requirements and bridged monobactams with such side chains have very low affinities for the enzyme. 

---