Fig. 1
Summary of enzymology studies: kinetic and mechanistic profiling for relebactam against P. aeruginosa AmpC. E: AmpC β-lactamase; EI: noncovalent AmpC β-lactamase/relebactam complex; E-I*: acylated AmpC β-lactamase/relebactam complex; I: relebactam; J: hydrolyzed product; kcat: turnover rate constant of β-lactamase inhibitor due to solvent water-mediated deacylation; Ki: dissociation constant for the initial step of noncovalent binding; Ki*: overall dissociation constant for initial binding and subsequent acylation/deacylation step; Kl: inactivation constant (if k− 2 ~ 0); k2: acylation or inactivation rate constant; k− 2: intramolecular deacylation or recovery rate constant; tn: turnover number (number of compound turnover needed for complete inhibition); k2/Ki: acylation efficiency. aInhibition kinetic parameter data are based on results from 4 trials. bRatio of acylation rate constant (k2) over Ki, a measure of acylation efficiency. c0.693/k− 2, the minimum estimate of half time for overall inhibitor dissociation. dRelebactam turnover number is based on data from 3 trials and with saturation time of 24 h (data for 2-h saturation time not shown due to similarity with 24-h data)