Thermokinetic evaluation of pyrrolidinedicarboxylic acid inhibiting cefalexin hydrolysis with metallo-β-lactamase L1 from Stenotrophomonas maltophilia

•Determined thermokinetic parameters of cefalexin hydrolysis with metallo-β-lactamase (MβL) L1.•First evaluated thermokinetic effect of the antibiotic hydrolysis with MβL that enzyme inhibitor caused.•Proposed a thermokinetic approach to identify inhibitor of MβLs.•Summarized that antibiotic hydrolysis with B1 and B3 MβLs has a higher value of E   and ΔH≠θ than that with B2 MβLs.

Given the enormous biomedical importance of screening inhibitor of the metallo-β-lactamases (MβLs), we determined the thermokinetic parameters of cefalexin hydrolysis with MβL L1 from Stenotrophomonas maltophilia in the absence and presence of 2,5-pyrrolidinedicarboxylic acid (PDA) as enzyme inhibitor. The presence of PDA caused a value decrease of the rate constant k, and a value increase of the apparent activation energy E (from 33.88 to 35.46 kJ mol−1), activation enthalpy ΔH≠θ (from 31.35 to 32.92 kJ mol−1), activation free energy ΔG≠θ and activation entropy ΔS≠θ (from −201.31 to −196.39 J mol−1 K−1) in comparison with the absence of PDA in the temperature range of 298.15–313.15 K, proposing that the changes of k, E  , ΔH≠θ and ΔS≠θ values can be employed to identify the inhibitors of MβLs.

Graphical abstractThe enzyme inhibitor PDA caused a value decrease of rate constant k, and a value increase of thermokinetic parameters of E  , ΔH≠θ, ΔG≠θ and ΔS≠θ during cefalexin hydrolysis with metallo-β-lactamase (MβL) L1.Figure optionsDownload full-size imageDownload as PowerPoint slide