On incubation of the chlorinated 6-spiroepoxypenicillin anilides (I) and (II) [formula: see text] with beta-lactamase 1 from Bacillus cereus, three distinct processes are observed. The inhibitors act as (a) substrates, the turnover of which respectively results in a single product, namely 6-substituted 2(H)-3,4-dihydro-1,4-thiazine, (b) a transiently inhibited enzyme complex, and finally (c) an irreversibly inactivated enzyme complex. Although differing only in their stereochemistry at one centre, the anilide (K) is a more potent irreversible inactivator of beta-lactamase I than is compound (II). Analysis of irreversibly inactivated beta-lactamase I by isoelectric focusing and inspection of peptide fragmentation maps indicated that irreversible inactivation appears to be accompanied by covalent modification. These studies reveal that the chlorinated 6-spiroepoxypenicillin anilide (I) is a mechanism-based beta-lactamase inhibitor.
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June 1991
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Research Article|
June 15 1991
Irreversible inactivation of β-lactamase I from Bacillus cereus by chlorinated 6-spiroepoxypenicillins
L Gledhill;
L Gledhill
1Department of Pharmaceutical Sciences, University of Nottingham, Nottingham NG7 2RD, U.K.
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P Williams;
P Williams
1Department of Pharmaceutical Sciences, University of Nottingham, Nottingham NG7 2RD, U.K.
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B W Bycroft
B W Bycroft
1Department of Pharmaceutical Sciences, University of Nottingham, Nottingham NG7 2RD, U.K.
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Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 1991 The Biochemical Society, London
1991
Biochem J (1991) 276 (3): 801–807.
Citation
L Gledhill, P Williams, B W Bycroft; Irreversible inactivation of β-lactamase I from Bacillus cereus by chlorinated 6-spiroepoxypenicillins. Biochem J 15 June 1991; 276 (3): 801–807. doi: https://doi.org/10.1042/bj2760801
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