This is primarily due to different contributions of Ala/Ser/Thr237, which contribute similarly to Ser70 in carbapenemases, but significantly less in the carbapenem-inhibited class A enzymes. A significant structural difference between carbapenemases and inhibited enzymes investigated here is the disulfide bond between Cys69 and Cys238 (Figure ). This disulfide bond constrains the protein backbone around the oxyanion hole, and so may influence its stabilization of the TI .