Theoretical Study on the Mechanism of the Acylate Reaction of β-Lactamase

Using density functional theory and a cluster approach, we study the reaction potential surface and compute Gibbs free energies for the acylate reaction of beta-lactamase with penicillin G, where the solvent effect is important and taken into consideration. Two reaction paths are investigated: one is a multi-step process with a rate-limit energy barrier of 19.1 kcal/mol, which is relatively small, and the reaction can easily occur; the other is a one-step process with a barrier of 45.0 kcal/mol, which is large and thus makes the reaction hard to occur. The reason why the two paths have different barriers is explained.

Automated summary

The study investigates the acylate reaction of beta-lactamase with penicillin G using density functional theory and a cluster approach. It reveals two reaction paths with different energy barriers: one relatively small and the reaction easily occurs, while the other large and making the reaction difficult to occur. The reason for the difference in barriers between the two paths is explained.