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
AN - SCOPUS:37049088775
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 -