The roles of the carboxy group in β-lactam antibiotics and lysine 234 in β-lactamase I

Andrew P. Laws, Nicola J. Layland, David G. Proctor, Michael I. Page

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The replacement of the C3 carboxylate in phenoxymethylpenicillin by a hydroxymethyl group and of the C4 carboxylate in cephalosporins by both a lactone and an aldehyde gives derivatives which are still good substrates for Bacillus cereus 569/H β-lactamase I. The enzyme rate-enhancement factors for the hydrolysis of the modified β-lactams vary from 104 to 106. All three modified substrates show bell-shaped (k cat/Km)-pH profiles indicative of two catalytically important ionising residues on the protein of pKa about 5 and 9. Although lysine 234 is a highly conserved residue in class A β-lactamases and has been traditionally thought to interact with the carboxylate of the β-lactam antibiotic, it is not responsible for the decrease in enzyme activity at high pH corresponding to the pKa of about 9.

LanguageEnglish
Pages17-21
Number of pages5
JournalJournal of the Chemical Society, Perkin Transactions 2
Issue number1
DOIs
Publication statusPublished - 1 Jan 1993

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Penicillinase
beta-Lactams
Lysine
Penicillin V
Bacillus cereus
Anti-Bacterial Agents
Enzyme activity
Lactones
Substrates
Cephalosporins
beta-Lactamases
Aldehydes
Hydrolysis
Derivatives
Enzymes
Proteins

Cite this

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The roles of the carboxy group in β-lactam antibiotics and lysine 234 in β-lactamase I. / Laws, Andrew P.; Layland, Nicola J.; Proctor, David G.; Page, Michael I.

In: Journal of the Chemical Society, Perkin Transactions 2, No. 1, 01.01.1993, p. 17-21.

Research output: Contribution to journalArticle

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