Rationalizing the Influence of the Binding Affinity on the Activity of Phosphoserine Phosphatases.

The Sabatier principle states that catalytic activity can be maximized when the substrate binding affinity is neither too strong nor too weak. Recent studies have shown that the activity of several hydrolases is maximized at intermediate values of the binding affinity (Michaelis-Menten constant: K m ). However, it remains unclear whether this concept of artificial catalysis is applicable to enzymes in general, especially for those which have evolved under different reaction environments. Herein, we show that the activity of phosphoserine phosphatase is also enhanced at an intermediate K m value of approximately 0.5 mM. Within our dataset, the variation of K m by three orders of magnitude accounted for a roughly 18-fold variation in the activity. Owing to the high phylogenetic and physiological diversity of our dataset, our results support the importance of optimizing K m for enzymes in general. On the other hand, a 77-fold variation in the activity was attributed to other physicochemical parameters, such as the Arrhenius prefactor of k cat , and could not be explained by the Sabatier principle. Therefore, while tuning the binding affinity according to the Sabatier principle is an important consideration, the K m value is only one of many physicochemical parameters which must be optimized to maximize enzymatic activity.