Page - (000053) - in Biomedical Chemistry: Current Trends and Developments

Figure 1.1.8: On top, the penicillin core structure is depicted. The β-lactam ring is highlighted in magenta, and in yellow the thiazolidine ring. R is a variable group and the structures on the bottom are those of the named antibiotics in this group. There are many other known possible groups that improve certain properties (absorption, hydrolysis, resistance, etc.). 1.1.5.3.1 Transpeptidase Mechanism Penicillin acts by irreversibly inhibiting the enzyme transpeptidase, which catalyses the formation of a peptide bond between an alanine and a terminal glycine of different polypeptides present in the cell wall. This halts the fabrication of new peptide crosslinks in the peptidoglycan layer, which degrades and eventually leads to cytolysis. The following steps constitute the catalysis mechanism of transpeptidase: 1. One peptide chain is linked to the enzyme via an acyl substitution reaction. The nucleophile is the hydroxyl from a serine residue of the transpeptidase and the leaving group is the C-terminal of alanine.