Inactivation of beta-lactamases from Enterobacter cloacae by monophosphams.
Amongst the monocyclic beta-lactam antibiotics, selected monophosphams were potent mechanism-based inactivators of the P99 and E2 cephalosporinases of Enterobacter cloacae. Inhibition of these enzymes was time-dependent with second order rate constants for inactivation of 100,000 to 20,000,000 l/mol/min. After incubation for 24 h at least 99% of the enzymatic activity was inhibited when enzyme was exposed to a ten-fold excess of inactivator. Amongst the monophosphams three classes of inhibitors were seen: irreversible inactivators as described above, transient inactivators and competitive (inhibitory) substrates.
Bush
K
K
Squibb Institute for Medical Research, Princeton, New Jersey 08543-4000.
Smith
S A
SA
Tanaka
S K
SK
Bonner
D P
DP
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002510:Cephalosporinase / Q000302:isolation & purification; D004754:Enterobacter / Q000201:enzymology*; D004755:Enterobacteriaceae / Q000201:enzymology*; D008826:Microbial Sensitivity Tests; D008997:Monobactams / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000302:isolation & purification
D000900:Anti-Bacterial Agents; D008997:Monobactams; D009943:Organophosphorus Compounds; D065093:beta-Lactamase Inhibitors; D002510:Cephalosporinase; D001618:beta-Lactamases