Abstract
Various cephalosporins, cefoxitin, moxalactam, imipenem and aztreonam were studied as substrates of six class C beta-lactamases. Nitrocefin, cephaloridine, cefazolin, cephalothin and cephalexin were good substrates, with kcat. values ranging from 27 to 5000 s-1. Cefuroxime, cefotaxime and cefoxitin exhibited low kcat. values (0.010-1.7 s-1) and low Km values, which suggested a rate-limiting deacylation. Imipenem and aztreonam were even poorer substrates (kcat. 2 x 10(-4)-3 x 10(-2) s-1) and, in the presence of a reporter substrate, behaved as transient inactivators. With moxalactam, biphasic kinetics were observed, indicating a possible rearrangement of the acyl-enzyme.
MeSH Terms
Aztreonam/metabolism
Cephalosporins/metabolism
Hydrolysis
Imipenem/metabolism
Kinetics
Moxalactam/metabolism
Substrate Specificity
beta-Lactamases/classification,metabolism
Chemicals
Cephalosporins
Imipenem
beta-Lactamases
Aztreonam
Moxalactam
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Galleni M
Laboratoire d'Enzymologie, Université de Liège, Sart Tilman, Belgium.
Amicosante G
Frère J M
References (18)
18 references, click to expand
-
The beta-lactamases of gram-negative bacteria and their possible physiological role.
Adv Microb Physiol. 1973;9:31-88
PMID: 4581138
-
A survey of the kinetic parameters of class C beta-lactamases. Penicillins.
Biochem J. 1988 Oct 1;255(1):119-22
PMID: 3264154
-
Purification and properties of a cephalosporinase from Enterobacter cloacae.
Antimicrob Agents Chemother. 1980 Dec;18(6):853-7
PMID: 6972193
-
Purification and properties of chromosomally mediated beta-lactamase from Citrobacter freundii GN7391.
J Gen Microbiol. 1980 Dec;121(2):449-56
PMID: 6973612
-
Isolation and properties of an inducible and a constitutive beta-lactamase from Pseudomonas aeruginosa.
J Gen Microbiol. 1982 Jan;128(1):155-9
PMID: 6806437
-
Interaction of azthreonam and related monobactams with beta-lactamases from gram-negative bacteria.
Antimicrob Agents Chemother. 1982 Sep;22(3):414-20
PMID: 6982680
-
The acyl-enzyme mechanism of beta-lactamase action. The evidence for class C Beta-lactamases.
Biochem J. 1982 Nov 1;207(2):315-22
PMID: 6818947
-
Kinetics and significance of the activity of the Sabath and Abrahams' beta-lactamase of Pseudomonas aeruginosa against cefotaxime and cefsulodin.
J Antimicrob Chemother. 1983 Feb;11(2):169-79
PMID: 6300016
-
Chromosomal beta-lactamases of Enterobacter cloacae are responsible for resistance to third-generation cephalosporins.
Antimicrob Agents Chemother. 1983 Jun;23(6):918-25
PMID: 6351733
-
beta-Lactamase inhibitors.
Med Res Rev. 1983 Oct-Dec;3(4):341-82
PMID: 6358721
-
Mechanism of inhibition of the PC1 beta-lactamase of Staphylococcus aureus by cephalosporins: importance of the 3'-leaving group.
Biochemistry. 1985 Feb 12;24(4):903-10
PMID: 3873255
-
The beta-lactamase of Enterobacter cloacae P99. Chemical properties, N-terminal sequence and interaction with 6 beta-halogenopenicillanates.
Biochem J. 1985 May 15;228(1):241-8
PMID: 2988516
-
6-beta-Iodopenicillanate as a probe for the classification of beta-lactamases.
Biochem J. 1986 Nov 1;239(3):575-80
PMID: 3030266
-
Properties of a class C beta-lactamase from Serratia marcescens.
Biochem J. 1986 Nov 1;239(3):581-6
PMID: 3548700
-
Automated analysis of enzyme inactivation phenomena. Application to beta-lactamases and DD-peptidases.
Biochem Pharmacol. 1987 Jul 15;36(14):2393-403
PMID: 3038122
-
Structure-activity relationships in the beta-lactam family: an impossible dream.
Biochem Pharmacol. 1988 Jan 1;37(1):125-32
PMID: 3276315
-
Sensitivity of Escherichia coli to various beta-lactams is determined by the interplay of outer membrane permeability and degradation by periplasmic beta-lactamases: a quantitative predictive treatment.
Mol Microbiol. 1987 Jul;1(1):29-36
PMID: 3330755
-
Enzymatic and immunological characterization of a new cephalosporinase from Enterobacter aerogenes.
Antimicrob Agents Chemother. 1977 Aug;12(2):201-5
PMID: 900918