Hydrolysis of 7-Substituted Cephalosporins catalysed by β-Lactamases I and II from Bacillus cereus and by Hydroxide Ion

Stephen C. Buckwell, Michael I. Page, Stephen G. Waley, Jethro L. Longridge

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1815-1821
Number of pages7
JournalJournal of the Chemical Society, Perkin Transactions 2
Issue number10
DOIs
Publication statusPublished - Oct 1988

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Bacillus cereus
Cephalosporins
Hydrolysis
Derivatives
Lactams
Chain length
Kinetic parameters
Rate constants
Catalysts
Substrates
Enzymes
hydroxide ion

Cite this

Buckwell, Stephen C. ; Page, Michael I. ; Waley, Stephen G. ; Longridge, Jethro L. / Hydrolysis of 7-Substituted Cephalosporins catalysed by β-Lactamases I and II from Bacillus cereus and by Hydroxide Ion. In: Journal of the Chemical Society, Perkin Transactions 2. 1988 ; No. 10. pp. 1815-1821.
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abstract = "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.",
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Hydrolysis of 7-Substituted Cephalosporins catalysed by β-Lactamases I and II from Bacillus cereus and by Hydroxide Ion. / Buckwell, Stephen C.; Page, Michael I.; Waley, Stephen G.; Longridge, Jethro L.

In: Journal of the Chemical Society, Perkin Transactions 2, No. 10, 10.1988, p. 1815-1821.

Research output: Contribution to journalArticle

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