Interaction of beta-lactamases I and II from Bacillus cereus with semisynthetic cephamycins. Kinetic studies.
The influence of C-6 alpha- or C-7 alpha-methoxylation of the beta-lactam ring in the catalytic action of class A and B beta-lactamases has been investigated. For this purpose the kinetic behaviour of beta-lactamases I (class A) and II (class B) from Bacillus cereus was analysed by using several cephamycins, moxalactam, temocillin and related antibiotics. These compounds behaved as poor substrates for beta-lactamase II, with high Km values and very low catalytic efficiencies. In the case of beta-lactamase I, the substitution of a methoxy group for a H atom at C-7 alpha or C-6 alpha decreased the affinity of the substrates for the enzyme. Furthermore, the acylation of cephamycins was completely blocked, whereas that of penicillins was slowed down by a factor of 10(4)-10(5), acylation being the rate-determining step of the process.
Departamento de Bioquímica y Biología Molecular, Facultad de Veterinaria, Universidad de León, Spain.
J
J
Martin Villacorta
P
P
Arriaga
J
J
Laynez
M
M
Menendez
D000215:Acylation; D000900:Anti-Bacterial Agents / Q000378:metabolism; D001409:Bacillus cereus / Q000201:enzymology*; D002384:Catalysis; D002513:Cephamycins / Q000378:metabolism*; D007700:Kinetics; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D002513:Cephamycins; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases