Interactions between beta-lactam antibiotics and isolated membranes of Streptococcus faecalis ATCC 9790.
The DD-carboxypeptidase-exchange membrane-bound enzyme in Streptococcus faecalis ATCC 9790 reacts with beta-lactam antibiotics to form complexes with rather long half-lives. Depending upon the antibiotic, the second-order rate constants for complex formation range from 0.75-560 M-1 S-1 (at 37 degrees C and in water) and the first-order rate constants for complex breakdown range from 1.3 to 26 x 10(-5) s-1 (at 37 degrees C and in 5 mM phosphate buffer pH 7.5). There are about 30 pmol of DD-carboxypeptidase-exchange enzyme per mg of membrane protein. The degradation products arising from benzylpenicillin are phenylacetylglycine and probably N-formyl-D-penicillamine. Isolated membranes also contain other penicillin binding sites (about 70 pmol/mg membrane protein). That part of benzylpenicillin which reacts with at least some of these latter sites is slowly degraded into penicilloic acid. Normal functioning of the DD-carboxypeptidase-exchange membrane-bound enzyme is important, if not essential, for cell growth. With the beta-lactam antibiotics tested inhibition of cell growth is mainly related to the rates of formation of the inactive enzyme-antibiotic complexes. The relationship, however, is not a direct one probably due to the competitive effect exerted by the other penicillin binding sites.
D001665:Binding Sites; D002268:Carboxypeptidases / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology*; D013293:Enterococcus faecalis / Q000201:enzymology*; D007700:Kinetics; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism*; D010400:Penicillin G / Q000031:analogs & derivatives / Q000378:metabolism*; D010406:Penicillins / Q000378:metabolism*; D011485:Protein Binding; D013329:Structure-Activity Relationship
D010406:Penicillins; D002268:Carboxypeptidases; D002267:Muramoylpentapeptide Carboxypeptidase; D010400:Penicillin G