Glycopeptide transpeptidase, penicillin inhibition

Ser residue in the active site of the enzyme acetylcholinesterase, irreversibly inhibiting the enzyme and preventing the transmission of nerve impulses (Fig. la). Iodoacetamide modifies Cys residues and hence may be used as a diagnostic tool in determining whether one or more Cys residues are required for enzyme activity (Fig. lb). The antibiotic penicillin irreversibly inhibits the glycopeptide transpeptidase enzyme that forms the cross-links in the bacterial cell wall by covalently attaching to a Ser residue in the active site of the enzyme (see Topic Al). 

Fig. 8.18 The antibiotic penicilhn inhibits the bacterial enzyme glycopeptide transpeptidase. The transpeptidase is a serine protease involved in cross-hnking components of bacterial cell walls and is essential for bacterial growth and survival. It normally cleaves the peptide bond between two D-alanine residues in a pol5 peptide. Penicillin contains a strained peptide bond within the (3-lactam ring that resembles the transition state of the normal cleavage reaction, and thus penicillin binds very readily in the enzyme active site. As the bacterial enzyme attempts to cleave this penicillin peptide bond, penicillin becomes irreversibly covalently attached to the enzyme s active site serine, thereby inactivating the enzyme.

The inhibition of bacterial cell wall synthesis by penicillin is a classic example of a medically significant inhibition of an enzymatic reaction. Which of the following statements about the inhibition of glycopeptide transpeptidase by penicillin is true ... 

FIGURE 44-2 Action of fi-iactam antibiotics in SUqyhytococcus aureus. The bacterial cell wall consists of glycopeptide polymers linked via bridges between amino acid side chains. In S. aureus, the bridge is (Gly),-D-Ala between lysines. The cross-linking is catalyzed by a transpeptidase, the enzyme that penicillins and cephalosporins inhibit. 

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