Enzymes play a vital role in the majority of biochemical reactions. Not only do they allow for life as we know it, they demonstrate remarkable specificity in many cases. How do enzymes work on only one chemical process, whereas hundreds of perhaps similar processes occur in the same general vicinity? Protein structure in general provides the answers. The primary, secondary, and tertiary structures of a protein all serve to direct the specific activity of an enzyme, but the region where the specific reaction is catalyzed is referred to as the active site.
If one could place a thin skin on the surface of an enzyme, the active site would invariably look like a pocket or cave in the surface. This structural feature is the reason why many textbooks show the mechanism of enzyme specificity as a lock-and-key model. The substrate, the molecule on which the enzyme acts, is the key that fits into the enzyme, which is the lock. Like a lock, only the correct key fits into it.
Looking at a more detailed perspective than is provided by this model, one can see that the selectivity of the active site is associated with its geometry. Intermolecular forces are present between the substrate and the components of the enzyme that are present in the active site.
For example, in order for hydrogen bonding to be able to take place, specific atoms must be present, as shown in Figure 1. In enzymes, normally there is either an O-H bond or an N-H bond when hydrogen bonding occurs. The other component of the hydrogen bond is a lone pair of electrons on either a nitrogen or oxygen. The strength of this interaction depends on the specific geometry present. The atoms must be both close enough to each other and in the correct direction from each other. Essentially, a hydrogen-bonding interaction requires that the three atoms involved form a straight (or nearly straight) line.
As there are many different types of active sites, it would be impossible to examine all of them here, but we can consider one important class of active sites, those that include metal ions. The inclusion of the metal ion in the enzyme may either be from strong coordinate covalent bonds , or via a looser association in the active site. When the metal is tightly bound, the protein is called a metalloenzyme . When the binding is not covalent, a metal-activated enzyme results. In either case, the metal ion is likely to be an important part of the active site.
One role that metal ions play in the active site of enzymes is to stabilize the charges that may be present. For example, the enzyme carbonic anhydrase, which plays the vital role of assisting the transport of carbon dioxide in the blood, is a metalloenzyme that includes zinc ions, Zn 2+ . This enzyme catalyzes the reaction of carbon dioxide with water to form hydrogen carbonate ions
CO 2 + H 2 O → HCO 3 − + H +
To speed this reaction, the zinc ion interacts with the water molecule to form a hydroxide, as shown in Figure 2. The small highly positively charged zinc ion is well suited to stabilize the negative charge of the hydroxide ion. Once formed, this ion reacts with carbon dioxide to form the hydrogen carbonate ion, which is released, and the Zn 2+ is now ready to catalyze another reaction.
Most active sites operate in ways that are somehow similar to those of this example. Portions of the enzyme in the active site bind to the substrate, facilitating its reaction, and then they release the product.
Dressler, D., and Potter, H. (1993). Discovering Enzymes. New York: Scientific American Library.
Kraut, J. (1988). "How Do Enzymes Work?" Science 242:533–540.