Assays for beta-lactamase activity and inhibition.
The ability, either innate or acquired, to produce beta-lactamases, enzymes capable of hydrolyzing the endocyclic peptide bond in beta-lactam antibiotics, would appear to be a primary contributor to the ever-increasing incidences of resistance to this class of antibiotics. To date, four distinct classes, A, B, C, and D, of beta-lactamases have been identified. Of these, enzymes in classes A, C, and D utilize a serine residue as a nucleophile in their catalytic mechanism while class B members are Zn2+-dependent for their function. Efforts have been and still continue to be made toward the development of potent inhibitors of these enzymes as a means to ensure the efficacy of beta-lactam antibiotics in clinical medicine. This chapter concerns procedures for the evaluation of the catalytic activity of beta-lactamases as a means to screen compounds for their inhibitory potency.
Viswanatha
Thammaiah
T
Department of Chemistry, University of Waterloo, W,Waterloo, Ontario, Canada.
Marrone
Laura
L
Goodfellow
Valerie
V
Dmitrienko
Gary I
GI
D001426:Bacterial Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000302:isolation & purification; D002614:Chelating Agents / Q000032:analysis; D004791:Enzyme Inhibitors / Q000032:analysis* / Q000494:pharmacology; D004795:Enzyme Stability; D004926:Escherichia coli / Q000201:enzymology*; D006801:Humans; D007700:Kinetics; D013053:Spectrophotometry; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000032:analysis* / Q000302:isolation & purification; D047090:beta-Lactams / Q000494:pharmacology
D001426:Bacterial Proteins; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D001618:beta-Lactamases