The calculations predict a reaction occurring in an enforced concerted manner with a very short lived intermediate, and subsequent protonation of the substrate by the catalytic cysteine as being rate limiting (in agreement with our measured D KIE, kH/kD = 1.42 for 2a). Observing the evolution of the most relevant distances of the reaction, it can be determined that the cysteine proton gradually approaches the substrate Cα, and is transferred only following cleavage of the respective carboxylate group. The reaction occurs in a highly similar fashion for both conformers. A crucial distinguishing feature between the two mechanisms appears to lie in a hydrogen bond formed between G190 and the cleaved carboxylate (Figure ). The respective hydrogen bond seems to fluctuate between larger values in case of the pro-S inversion (Figure ).