Examples of Enzymatic Reactions:- Hexokinase Undergoes Induced Fit on Substrate Binding
Yeast hexokinase (Mr 107,862) is a bisubstrate enzyme that catalyzes the reversible reaction
ATP and ADP always bind to enzymes as a complex with the metal ion Mg+2.
FIGURE 6–22 Induced fit in hexokinase. (a) Hexokinase has a U-shaped structure (PDB ID 2YHX). (b) The ends pinch toward each other in a conformational change induced by binding of D-glucose (red) (derived from PDB ID 1HKG and PDB ID 1GLK).
The hydroxyl at C-6 of glucose (to which the 
γ-phosphoryl of ATP is transferred in the hexokinase reaction) is similar in chemical reactivity to water, and water freely enters the enzyme active site. Yet hexokinase favors the reaction with glucose by a factor of 106. The enzyme can discriminate between glucose and water because of a conformational change in the enzyme when the correct substrates binds (Fig. 6–22). Hexoki nase thus provides a good example of induced fit. When glucose is not present, the enzyme is in an inactive con formation with the active-site amino acid side chains out of position for reaction. When glucose (but not water) and Mg ATP bind, the binding energy derived from this interaction induces a conformational change in hexokinase to the catalytically active form. This model has been reinforced by kinetic studies. The five-carbon sugar xylose, stereochemically similar to glucose but one carbon shorter, binds to hexokinase but in a position where it cannot be phosphorylated. Nevertheless, addition of xylose to the reaction mix ture increases the rate of ATP hydrolysis. Evidently, the binding of xylose is sufficient to induce a change in hexokinase to its active conformation, and the enzyme is thereby “tricked” into phosphorylating water. The hexokinase reaction also illustrates that enzyme specificity is not always a simple matter of binding one com pound but not another. In the case of hexokinase, specificity is observed not in the formation of the ES complex but in the relative rates of subsequent catalytic steps. Water is not excluded from the active site, but reaction rates increase greatly in the presence of the functional phosphoryl group acceptor (glucose).
Induced fit is only one aspect of the catalytic mechanism of hexokinase—like chymotrypsin, hexokinase uses several catalytic strategies. For example, the active site amino acid residues (those brought into position by the conformational change that follows substrate binding) participate in general acid-base catalysis and transition-state stabilization.
