This disulfide has been identified as a potentially essential for the carbapenemase activity of SME-1, and mutations that disrupt the disulfide bond affect enzyme stability in both NMC-A and SFC-1 carbapenemases . The disulfide itself does not confer carbapenem-hydrolyzing activity upon all Class A enzymes, however, see e.g. GES-5 . To investigate its role in TI stabilization, the SFC-1 Cys238Gly mutant was constructed (Gly238 is observed in the carbapenem-inhibited enzyme BlaC). Reaction simulations were carried out for the SFC-1 Cys238Gly mutant, with the 6-hydroxyethyl dihedral restrained to Position II (see next section), enabling a direct comparison with wild type SFC-1 in which this group adopts the same orientation. The calculated barrier for SFC-1 Cys238Gly is 13.5 kcal/mol, 5.4 kcal/mol higher than for the wild type enzyme, confirming the importance of the disulfide bond in modulating TI stabilization.