The β-lactam hydrolysis mechanism starts with acylation which, in class A enzymes, occurs through nucleophilic attack of the active site Ser70 on the carbonyl carbon of the β-lactam ring. In carbapenem-inhibited class A β-lactamases, including TEM-1, SHV-1, BlaC and CTX-M-16, formation of a long-lasting carbapenem acyl-enzyme complex (Scheme 1B) is the reason for inhibition: the deacylation rate in these enzymes is low . In contrast, enzymes such as KPC-2 (now widely distributed in K. pneumoniae in the clinic), SFC-1, NMC-A and SME-1 have the ability to deacylate significantly faster and confer bacterial resistance through efficient deactivation of carbapenem antibiotics. Scheme 1: Proposed carbapenem deacylation mechanism for class A β-lactamases . In the acylenzyme (A) proton transfer from the DW to Glu166, with subsequent nucleophilic attack on the carbapenem acylenzyme carbonyl carbon, results in formation of a tetrahedral intermediate (B).