Reaction of Lys-Tyr-Lys Triad Mimics with Benzylpenicillin: Insight into the Role of Tyr150 in Class C β-Lactamase

Small and simple molecules mimicking a Lys-Tyr-Lys triad and some ‘mutant’ derivatives were designed and synthesized. These compounds react with benzylpenicillin in water (75 mM phosphate buffer, pH 7), apparently through general base assistance by the phenolic moiety. Class C β-lactamase has a Lys-Tyr-Lys triad in its active site, and our finding gives some insight into the role of this triad in the enzymatic β-lactam hydrolysis mechanism.