Looking at the energy profile (c.f. Fig 3 ), we can see that the decay of Cpd I is an efficient process with a barrier of ~9.6 kcal/mol followed by a multistep process that involves Cpd I→ IM1→IM2→product. As such, our QM/MM calculations qualitatively agree with the conclusions of Grant et al. It is apparent that our calculations provide compelling evidence that the peculiar mechanism of substrate decarboxylation in OleT is virtually a concerted process (barrier ~2 kcal/mol; cf. Figure ) and the active site topology with its protonated His85 residue, is the root cause for the decarboxylation, whereas the common rebound process is blocked by an organized His85-water dyad (see W1,2 and H85 in IM1 cf. Figure ).