9.2.1 Enzyme–Substrate Complex

The key factor that sets enzymatic reactions apart from other catalyzed reactions is the formation of an enzyme–substrate complex, (E · S). Here, substrate binds with a specific active site of the enzyme to form this complex.⁷ Figure 9-4 shows a schematic of the enzyme chymotrypsin (MW = 25,000 Daltons), which catalyzes the hydrolytic cleavage of polypeptide bonds. In many cases the enzyme’s active catalytic sites are found where the various folds or loops interact. For chymotrypsin, the catalytic sites are noted by the amino acid numbers 57, 102, and 195 in Figure 9-4. Much of the catalytic power is attributed to the binding energy of the substrate to the enzyme through multiple bonds with the specific functional groups on the enzyme (amino side chains, metal ions). The interactions that stabilize the enzyme–substrate complex are hydrogen bonding and hydrophobic, ionic, and London van der Waals forces. If the enzyme is exposed to extreme temperatures or pH environments (i.e., both high and low pH values), it may unfold, losing its active sites. When this occurs, the enzyme is said to be denatured. See Problem P9-13_B.

Figure 9-4. Enzyme chymotrypsin.

There are two models for substrate-enzyme interactions: the lock and key model and the induced fit model, both of which are shown in Figure 9-5. For many years the lock and key model was preferred because of the sterospecific effects of one enzyme acting on one substrate. However, the induced fit model is the more useful model. In the induced fit model, both the enzyme molecule and the substrate molecules are distorted. These changes in conformation distort one or more of the substrate bonds, thereby stressing and weakening the bond to make the molecule more susceptible to rearrangement or attachment.

Figure 9-5. Two models for enzyme-substrate interaction.

There are six classes of enzymes and only six:

More information about enzymes can be found on the following two Web sites: http://us.expasy.org/enzyme/ and www.chem.qmw.ac.uk/iubmb/enzyme. These sites also give information about enzymatic reactions in general.