Hydrolysis of 6-Alkyl Penicillins catalysed by β-Lactamase I from Bacillus cereus and by Hydroxide ion

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

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Second-order rate constants for the hydroxide ion-catalysed hydrolysis of 6-alkyl penicillins are independent of the length of the alkyl side-chain and replacement of the amido by an amino group decreases the susceptibility to nucleophilic attack on 6-aminopenicillanic acid only three-fold. B. cereus β-lactamase I catalyses the hydrolysis of 6-alkyl penicillins with values of kcat/Km which are at least 50-fold greater than that shown by 6-aminopenicillanic acid. For the enzyme-catalysed reaction k cat/Km increases with increasing chain length, reaching a maximum with hexylpenicillin, and then decreases. The binding energy of the alkyl group is weak, only 1.45 kJ mol-1 per methylene residue. Although there appears to be a recognition site for the amido group there is no specific pocket in β-lactamase I for the recognition of hydrophobic residues in the 6-acylamido side-chain of penicillins.

LanguageEnglish
Pages1809-1813
Number of pages5
JournalJournal of the Chemical Society, Perkin Transactions 2
Issue number10
DOIs
Publication statusPublished - Oct 1988

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Bacillus cereus
Penicillinase
Penicillins
Hydrolysis
Binding energy
Chain length
Rate constants
Enzymes
hydroxide ion
aminopenicillanic acid

Cite this

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title = "Hydrolysis of 6-Alkyl Penicillins catalysed by β-Lactamase I from Bacillus cereus and by Hydroxide ion",
abstract = "Second-order rate constants for the hydroxide ion-catalysed hydrolysis of 6-alkyl penicillins are independent of the length of the alkyl side-chain and replacement of the amido by an amino group decreases the susceptibility to nucleophilic attack on 6-aminopenicillanic acid only three-fold. B. cereus β-lactamase I catalyses the hydrolysis of 6-alkyl penicillins with values of kcat/Km which are at least 50-fold greater than that shown by 6-aminopenicillanic acid. For the enzyme-catalysed reaction k cat/Km increases with increasing chain length, reaching a maximum with hexylpenicillin, and then decreases. The binding energy of the alkyl group is weak, only 1.45 kJ mol-1 per methylene residue. Although there appears to be a recognition site for the amido group there is no specific pocket in β-lactamase I for the recognition of hydrophobic residues in the 6-acylamido side-chain of penicillins.",
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Hydrolysis of 6-Alkyl Penicillins catalysed by β-Lactamase I from Bacillus cereus and by Hydroxide ion. / Buckwell, Stephen C.; Page, Michael I.; Longridge, Jethro L.

In: Journal of the Chemical Society, Perkin Transactions 2, No. 10, 10.1988, p. 1809-1813.

Research output: Contribution to journalArticle

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AU - Page, Michael I.

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N2 - Second-order rate constants for the hydroxide ion-catalysed hydrolysis of 6-alkyl penicillins are independent of the length of the alkyl side-chain and replacement of the amido by an amino group decreases the susceptibility to nucleophilic attack on 6-aminopenicillanic acid only three-fold. B. cereus β-lactamase I catalyses the hydrolysis of 6-alkyl penicillins with values of kcat/Km which are at least 50-fold greater than that shown by 6-aminopenicillanic acid. For the enzyme-catalysed reaction k cat/Km increases with increasing chain length, reaching a maximum with hexylpenicillin, and then decreases. The binding energy of the alkyl group is weak, only 1.45 kJ mol-1 per methylene residue. Although there appears to be a recognition site for the amido group there is no specific pocket in β-lactamase I for the recognition of hydrophobic residues in the 6-acylamido side-chain of penicillins.

AB - Second-order rate constants for the hydroxide ion-catalysed hydrolysis of 6-alkyl penicillins are independent of the length of the alkyl side-chain and replacement of the amido by an amino group decreases the susceptibility to nucleophilic attack on 6-aminopenicillanic acid only three-fold. B. cereus β-lactamase I catalyses the hydrolysis of 6-alkyl penicillins with values of kcat/Km which are at least 50-fold greater than that shown by 6-aminopenicillanic acid. For the enzyme-catalysed reaction k cat/Km increases with increasing chain length, reaching a maximum with hexylpenicillin, and then decreases. The binding energy of the alkyl group is weak, only 1.45 kJ mol-1 per methylene residue. Although there appears to be a recognition site for the amido group there is no specific pocket in β-lactamase I for the recognition of hydrophobic residues in the 6-acylamido side-chain of penicillins.

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