The importance of the negative charge of beta-lactam compounds for the inactivation of the active-site serine DD-peptidase of Streptomyces R61.
The interaction between the Streptomyces R61 penicillin-sensitive DD-peptidase and deacetyl-cephalosporin C or its lactone derivative has been studied at different pH values. The results show the importance of an enzyme group of pK approximately equal to 9 which might form an ion pair with the free carboxylate of the former compound. This electrostatic interaction is shown to contribute to the formation of the first, non-covalent enzyme-inactivator complex by a factor of at least 50.
Service de Microbiologie, Université de Liège, Belgium.
L
L
Varetto
J M
JM
Frère
J M
JM
Ghuysen
D001665:Binding Sites; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002511:Cephalosporins / Q000378:metabolism* / Q000494:pharmacology; D004563:Electrochemistry; D004789:Enzyme Activation / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D006878:Hydroxides / Q000378:metabolism; D007700:Kinetics; D007783:Lactones / Q000378:metabolism* / Q000494:pharmacology; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; D013050:Spectrometry, Fluorescence; D013302:Streptomyces / Q000201:enzymology*
D002511:Cephalosporins; D006878:Hydroxides; D007783:Lactones; C025071:deacetylcephalosporin C; D002268:Carboxypeptidases; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase