The reversible deactivation of beta-lactamase from Staphylococcus aureus by quinacillin and cephaloridine and its modification by antibodies.
The effect of antibody on the reversible deactivation of the beta-lactamase (penicillin amino-beta-lactamhydrolase, EC 3.5.2.6) from Staphylococcus aureus has been studied using quinacillin and cephaloridine as substrates. The latter has been shown to exhibit the characteristics of an A-type substrate Citri, N., Samuni, A. and Zyk, N. (1976) Proc. Natl. Acad. Sci. U.S.A. 73, 1048-1052) and reversibly to lower the activity of the enzyme towards benzylpenicillin in a manner analogous to quinacillin. Both divalent and monovalent antibodies reduce the activity of the lactamase to 60% of the native value in the absence of substrate. The reduction by monovalent antibody is slow (t1/2 approximately equal to 25 min). Both divalent and monovalent antibodies modify the time-course of reversible deactivation independently of being added before or subsequent to deactivation by substrate. The full recovery of activity is delayed in the case of quinacillin and accelerated for cephaloridine. The activity against benzylpenicillin in the deactivated states is unaffected. These effects are shown to reflect the changed rates of hydrolysis of the two substrates in the presence of antibody. The effect of antibody is mediated by minor conformational change. Continuous assays for following the hydrolysis of quinacillin and cephaloridine by optical rotation are reported.
D002509:Cephaloridine / Q000378:metabolism / Q000494:pharmacology*; D000939:Epitopes; D007106:Immune Sera / Q000494:pharmacology*; D007140:Immunoglobulin Fab Fragments; D007700:Kinetics; D010400:Penicillin G / Q000378:metabolism; D010405:Penicillinase / Q000276:immunology; D010406:Penicillins / Q000378:metabolism / Q000494:pharmacology*; D011487:Protein Conformation; D013211:Staphylococcus aureus / Q000201:enzymology*; D065093:beta-Lactamase Inhibitors
D000939:Epitopes; D007106:Immune Sera; D007140:Immunoglobulin Fab Fragments; D010406:Penicillins; D065093:beta-Lactamase Inhibitors; C011097:quinacillin; D010405:Penicillinase; D002509:Cephaloridine; D010400:Penicillin G