Kinetic parameters are reported for the Bacillus cereus β-lactamase I- and β-lactamase II-catalysed hydrolysis of a series of thirty-seven cephalosporins substituted in the 7-position. These are compared with the second-order rate constants for the hydroxide ion-catalysed hydrolysis of these derivatives. There is no significant dependence of the rate of the base-catalysed hydrolysis upon the nature of the side-chain substituent. For β-lactamase I, kcat/Km varies over 2 x 105 but for β-lactamase II the variation with substituents is only 10. For alkyl substituents, kcat/Km increases with chain length and passes through a maximum, for β-lactamase I this is with the undecyl derivative and for β-lactamase II the octylcephalosporin. For β-lactamase I, but not for β-lactamase II, the t-butylcephalosporin is a very poor substrate. There is no evidence for a significant cavity in either enzyme to host aromatic residues. An ionised carboxylate residue on the side-chain significantly reduces reactivity with β-lactamase I but not β-lactamase II. It is suggested that a carboxy group on β-lactamase I acts as a general catalyst facilitating β-lactam C-N bond fission.
|Number of pages||7|
|Journal||Journal of the Chemical Society, Perkin Transactions 2|
|Publication status||Published - Oct 1988|