In this work, we evidenced an interplay between reactivity and conformational fluctuations in the active site, as key aspects of the reaction (e.g. nature of the general base) are intimately coupled to conformational fluctuations of the active site, that modulate the distance between reactive partners. Distinct conformations of the active site appear preorganized to favor different mechanisms. This echos recent works that increasingly suggest an interplay between conformational fluctuations and catalytic activity in enzymes. This work thus underlines the importance to perform extensive conformational exploration of the reactant state of a reactive complex before mechanistic investigations.