Oh

Glucose 6-phosphate

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).

ATP and ADP always bind to enzymes as a complex with the metal ion Mg2 + .

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 y-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). Hexokinase thus provides a good example of induced fit. When glucose is not present, the enzyme is in an inactive conformation 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 mixture 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 compound 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).

Lose 10 Pounds Naturally

Lose 10 Pounds Naturally

Studies show obesity may soon overtake tobacco as the leading cause of death in America. Are you ready to drop those extra pounds you've been carrying around? Awesome. Let's start off with a couple positive don't. You don't need to jump on a diet craze and you don't need to start exercising for hours each day.

Get My Free Ebook


Post a comment