The diversity of the catalytic properties of class A β-lactamases

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Abstract
The catalytic properties of four class A .beta.-lactamases were studied with 24 differnt substrates. They exhibit a wide range of variation. Similarly, the amino acid sequences are also quite different. However, no relationships were found between the sequence similarities and the substrate profiles. Lags and bursts were observed with various compounds containing a large sterically hindered side chain. As a group, the enzyms could be distinguished from the class C .beta.-lactamase on the basis ofthe kcat, values for several substrates, particularly oxacillin, cloxacillin and carbenicillin. Surprisingly, that distinction was impossible with the kcat/Km values, which represent the rates of acylation of the active-site serine residue by the .beta.-lactam. For several cephalosporin substrates (e.g. cefuroxime and cefotaxime) class A enzymes consistently exhibited higher kcat values than class C enzymes, thus belying the usual distinction between ''penicillinases'' and ''cephalosporinases''. The problem of the repartition of class A .beta.-lactamases into sub-classes is discussed.