Electrostatic Origin of the Catalytic Power of Enzymes and the Role of Preorganized Active Sites

Enzymatic reactions are involved in most biological processes. Thus, there is a major practical and fundamental interest in finding out what makes enzymes so efficient. Many crucial pieces of this puzzle were provided by biochemical and structural studies (1). Yet, as will be shown below, the actual reason for the catalytic power of enzymes is not widely understood. It is clearly not explained by the statement that "the enzyme binds the transition state stronger than the ground state" because the real question is how the differential binding can be accomplished. Similarly, it is not true that "evolution can use any factor to accelerate reactions." This review uses energy considerations and the results of computational studies to clarify open questions about enzyme catalysis.