FIGURE 6.

Molecular modeling of PenA and PenI with imipenem. A, Michaelis-Menten complex of PenA (cyan) with IMI (green) shows that the carbonyl of IMI is oriented toward the oxyanion hole, the backbone amides of Ser-70 and Thr-237. B, Michaelis-Menten complex of PenI (orange) with IMI (green) reveals the different conformation of Tyr-105 compared with PenA model. C, Δ² isoform of IMI (green) with PenA (cyan) reveals the carbonyl of IMI is within the oxyanion hole and in a position favorable for deacylation. D, Δ² isoform of IMI (green) with PenI (orange) demonstrates that the carbonyl of IMI is outside of oxyanion hole. Water molecules (not shown) are present near Arg-220; thus IMI is in a favorable orientation for tautomerization of its C₂–C₃ double bond for generation of the more stable Δ¹ isoform.