Hydrolysis of 3-substituted cephalosporins catalysed by β-lactamases I and II from Bacillus cereus and by hydroxide ion

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

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Second-order rate constants for the alkaline hydrolysis of 3-thiol substituted cephalosporins are independent of the pKa of the thiol over a pKa range of 9. If there is a leaving group at C-3′ it is expelled after the β-lactam ring is opened and the expulsion of the leaving group does not enhance the rate of β-lactam C-N bond fission. The zinc enzyme β-lactamase II is about a 100-fold better catalyst than the serine enzyme β-lactamase I for the hydrolysis of the same cephalosporin. The second-order rate constant kcat/Km for both β-lactamase enzymes shows no dependence on the nature of the substituent at C-3′ which is not explicable by the different chemical reactivity of the cephalosporins. There is no evidence for a significant recognition site in either enzyme for the C-3′ substituent. The kinetic parameters k cat and Km for the β-lactamase I-catalysed hydrolysis may be complicated by the formation of intermediates.

Original languageEnglish
Pages (from-to)1823-1827
Number of pages5
JournalJournal of the Chemical Society, Perkin Transactions 2
Issue number10
DOIs
Publication statusPublished - Oct 1988

Fingerprint

Bacillus cereus
Cephalosporins
Hydrolysis
Lactams
Enzymes
Sulfhydryl Compounds
Rate constants
Chemical reactivity
Kinetic parameters
Serine
Zinc
Catalysts
hydroxide ion

Cite this

Buckwell, Stephen C. ; Page, Michael I. ; Longridge, Jethro L. ; Waley, Stephen G. / Hydrolysis of 3-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. 1823-1827.
@article{9f83ddba7fc94c068802e17770b04391,
title = "Hydrolysis of 3-substituted cephalosporins catalysed by β-lactamases I and II from Bacillus cereus and by hydroxide ion",
abstract = "Second-order rate constants for the alkaline hydrolysis of 3-thiol substituted cephalosporins are independent of the pKa of the thiol over a pKa range of 9. If there is a leaving group at C-3′ it is expelled after the β-lactam ring is opened and the expulsion of the leaving group does not enhance the rate of β-lactam C-N bond fission. The zinc enzyme β-lactamase II is about a 100-fold better catalyst than the serine enzyme β-lactamase I for the hydrolysis of the same cephalosporin. The second-order rate constant kcat/Km for both β-lactamase enzymes shows no dependence on the nature of the substituent at C-3′ which is not explicable by the different chemical reactivity of the cephalosporins. There is no evidence for a significant recognition site in either enzyme for the C-3′ substituent. The kinetic parameters k cat and Km for the β-lactamase I-catalysed hydrolysis may be complicated by the formation of intermediates.",
author = "Buckwell, {Stephen C.} and Page, {Michael I.} and Longridge, {Jethro L.} and Waley, {Stephen G.}",
year = "1988",
month = "10",
doi = "10.1039/P29880001823",
language = "English",
pages = "1823--1827",
journal = "Journal of the Chemical Society, Perkin Transactions 2",
issn = "0300-922X",
publisher = "Chemical Society",
number = "10",

}

Hydrolysis of 3-substituted cephalosporins catalysed by β-lactamases I and II from Bacillus cereus and by hydroxide ion. / Buckwell, Stephen C.; Page, Michael I.; Longridge, Jethro L.; Waley, Stephen G.

In: Journal of the Chemical Society, Perkin Transactions 2, No. 10, 10.1988, p. 1823-1827.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Hydrolysis of 3-substituted cephalosporins catalysed by β-lactamases I and II from Bacillus cereus and by hydroxide ion

AU - Buckwell, Stephen C.

AU - Page, Michael I.

AU - Longridge, Jethro L.

AU - Waley, Stephen G.

PY - 1988/10

Y1 - 1988/10

N2 - Second-order rate constants for the alkaline hydrolysis of 3-thiol substituted cephalosporins are independent of the pKa of the thiol over a pKa range of 9. If there is a leaving group at C-3′ it is expelled after the β-lactam ring is opened and the expulsion of the leaving group does not enhance the rate of β-lactam C-N bond fission. The zinc enzyme β-lactamase II is about a 100-fold better catalyst than the serine enzyme β-lactamase I for the hydrolysis of the same cephalosporin. The second-order rate constant kcat/Km for both β-lactamase enzymes shows no dependence on the nature of the substituent at C-3′ which is not explicable by the different chemical reactivity of the cephalosporins. There is no evidence for a significant recognition site in either enzyme for the C-3′ substituent. The kinetic parameters k cat and Km for the β-lactamase I-catalysed hydrolysis may be complicated by the formation of intermediates.

AB - Second-order rate constants for the alkaline hydrolysis of 3-thiol substituted cephalosporins are independent of the pKa of the thiol over a pKa range of 9. If there is a leaving group at C-3′ it is expelled after the β-lactam ring is opened and the expulsion of the leaving group does not enhance the rate of β-lactam C-N bond fission. The zinc enzyme β-lactamase II is about a 100-fold better catalyst than the serine enzyme β-lactamase I for the hydrolysis of the same cephalosporin. The second-order rate constant kcat/Km for both β-lactamase enzymes shows no dependence on the nature of the substituent at C-3′ which is not explicable by the different chemical reactivity of the cephalosporins. There is no evidence for a significant recognition site in either enzyme for the C-3′ substituent. The kinetic parameters k cat and Km for the β-lactamase I-catalysed hydrolysis may be complicated by the formation of intermediates.

UR - http://www.scopus.com/inward/record.url?scp=37049088775&partnerID=8YFLogxK

U2 - 10.1039/P29880001823

DO - 10.1039/P29880001823

M3 - Article

SP - 1823

EP - 1827

JO - Journal of the Chemical Society, Perkin Transactions 2

JF - Journal of the Chemical Society, Perkin Transactions 2

SN - 0300-922X

IS - 10

ER -