Inactivation of the RTEM beta-lactamase from Escherichia coli. Interaction of penam sulfones with enzyme.
The characteristics of the reaction of a number of mechanism-based inactivators of the RTEM beta-lactamase have suggested that a common mechanistic pathway may be followed by many of these compounds. These ideas have been tested by the synthesis and evaluation of some penam sulfones as beta-lactamase inactivators. The sulfones of poor beta-lactamase substrates are, as predicted, potent inactivators of the enzyme. A unique serin residue (Ser-70) is labeled by quinacillin sulfone, and it is likely that this serine acts nucleophilically in the normal hydrolytic reaction of the beta-lactamase to form an acyl-enzyme intermediate.
D000596:Amino Acids / Q000032:analysis; D001665:Binding Sites; D004926:Escherichia coli / Q000201:enzymology*; D007700:Kinetics; D010406:Penicillins / Q000494:pharmacology*; D010446:Peptide Fragments / Q000032:analysis; D010957:Plasmids; D011485:Protein Binding; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors
D000596:Amino Acids; D010406:Penicillins; D010446:Peptide Fragments; D013450:Sulfones; D065093:beta-Lactamase Inhibitors