The structure of the surface domain of the BlaR1 protein of Staphylococcus aureus, a beta-lactam antibiotic sensor/signal transducer, is essentially identical to that of the class D beta-lactamases, which are antibiotic resistance enzymes. Both proteins have an unusual N-carboxylated lysine within their active sites, which promotes a serine for acylation by the antibiotic. N-Carboxylated lysine also catalyzes hydrolytic deacylation of the acyl-enzyme species in the beta-lactamase. The situation with the BlaR1 protein is different in that on acylation of serine N-carboxylated lysine experiences decarboxylation, whereby the process is arrested in the acyl-protein stage. As such, BlaR1 experience acylation by the antibiotic that it senses, an event that enjoys longevity for at least the duration of one bacterial generation. We report herein the production of S-(4-butanoate)-cysteine, as a surrogate of N-carboxylated lysine at position 392 of the BlaR1 protein. This unnatural amino acid cannot experience N-decarboxylation. We observed that BlaR1 protein modified at position 392 by S-(4-butanoate)-cysteine behaves as a reasonable beta-lactamase. We have shown herein that the mechanistic basis for the BlaR1 protein serving as a receptor is solely its ability to undergo N-decarboxylation of the active site lysine on protein acylation by its antibiotic ligand.