Enzymology of metallo-B-lactamases



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Texas Tech University


Pathogenic bacteria become resistant to penidlhns and cephalosporins through acquisition of a gene encoding the enzyme p -lactamase. (Livermore, 1991) Four classes distinguish P-lactamases as either active site serine hydrolases (class A, C and D) or zinc containmg hydrolases (class B). The class C enzyme is further distmguished from the others by being membrane bound. These bacterial enzymes catalyze the hydrolysis of the p-lactam amide group of their substrates. The class A enzyme has been studied extensively with respect to its structure, hydrolysis mechanism and inhibition. Class A enzymes proceed through an acyl-enzyme intermediate involving an active site serine residue (Fisher et al., 1980). Many substrate and transition state analogs have exhibited inhibitory effects on the class A enzyme and are used medicinally as antibiotic supplements (Wainwright, 1990). Until recently, the class B P-lactamases did not demand such study as their class A counterparts. Now, more and more clinical cases of carbapenem resistant bacteria containing the class B, zinc-requiring enzyme has caused some concern (Payne, 1993). The increased occurrence of noxious gram-positive resistant bacteria has sparked a renewed investigation into p-lactamase enzymology.



Mechanism of action, Beta lactamases, Cephalosporins