Structure of the complex with aztreonam

Models were built (Figs. 3 and 4) of the Michaelis complex (3b), the hemiacetal transition state (3c), the acyl enzyme (3d) and the deacylation step. All of these models could nicely be accommodated in the crystal structure without changing any protein coordinates except for those of the catal)dic serine. 

In the case of penicillin G, the outward rotation about the C3-C4 bond can occur vithout conflict with protein side chains. It relaxes the strained conformation along this bond previously enforced by the four-membered ring. Moreover, this rotation improves hydrophobic contact of the dimethyl and the sulfur part of the thiazolidine ring of penicillin with two leucine side chains, thus offering an additional driving force for the outward rotation. Experimental evidence is provided by the observed rotation of 35.2° in this direction about the C3-C4 bond that occurs in the acyl-enzyme complex formed between benzyl penicillin and a mutant class A beta-lactamase (RTEM-1) blocked in deacylation [9]. 

5 Structure-Based Design of Potent Beta-Lactamase Inhibitors 

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