Figure 1. The effect on free energy of substrate-induced conformational change leading to enzymatic activation. The free energy of the enzyme–substrate ground state and transition state, and the free energy of the catalytic rate constant k_cat and k_cat/K_M are indicated. Features of the low probability state E–S^‡ are shown in blue. (a) The substrate-induced changes stabilize the ground state and transition state by an equal amount . The free energy of k_cat is uneffected, while that of k_cat/K_M is lowered and this rate increases. (b) The transition state is stabilized more than the ground state. The free energy of both k_cat and k_cat/K_M is lowered, and both rates increase.

Figure 2. Thermodynamic binding cycle to represent an induced-fit process. In the physical process, the substrate S binds E and induces the change to the catalytically active form E_act. The energetically equivalent, albeit hypothetical, process factors out the conformational activation of the inactive enzyme E to the active form E_act with the equilibrium K_act << 1.0. This step is followed by S binding E_act with the dissociation constant K_S.

Figure 3. Schematic representation of a substrate-induced fit that confers specificity because the specific changes in the enzyme E exist into the transition state. The enzyme structure in the transition state of the good substrate produces an optimum environment for catalysing the chemical step and has high catalytic efficiency. The enzyme form in the transition state for the poor substrate differs and solvates the bond making/bond breaking in the transition state less well. The chemical transformation is rate-limiting for both substrates and occurs in the dark blue moiety of the good substrate. Binding of the poor substrate, which is the reactive fragment of the good substrate, induces a small closing of the enzyme active site. The change in E to form the optimum transition state environment requires the additional binding interactions of the light blue fragment.