Lock-and-key model of enzyme action

FIGURE 13.40 In the lock-and-key model of enzyme action, the correct substrate is recognized by its ability to fit into the active site like a key into a lock. In a refinement of this model, the enzyme changes its shape slightly as the key enters. 

One of the earliest, simplest, and best-known examples of this concept is the lock-and-key model of enzyme action hrst proposed by German chemist Emil Fischer (1852-1919) in 1894. While it has been significantly modihed since that time, the general mode of action suggested by Fischer is probably generally correct for most types of enzyme action. According to the lock-and-key model, illustrated below. 

The topologically defined region(s) on an enzyme responsible for the binding of substrate(s), coenzymes, metal ions, and protons that directly participate in the chemical transformation catalyzed by an enzyme, ribo-zyme, or catalytic antibody. Active sites need not be part of the same protein subunit, and covalently bound intermediates may interact with several regions on different subunits of a multisubunit enzyme complex. See Lambda (A) Isomers of Metal Ion-Nucleotide Complexes Lock and Key Model of Enzyme Action Low-Barrier Hydrogen Bonds Role in Catalysis Yaga-Ozav /a Plot Yonetani-Theorell Plot Induced-Fit Model Allosteric Interaction... 

LINKED FUNCTIONS LOCK-AND-KEY MODEL OF ENZYME ACTION... 

The lock-and-key model of enzyme action, introduced by Emil Fischer in 1890, partially accounts for enzyme specificity. Each enzyme binds to a single type... 

Enzymes are biological catalysts. They enhance reaction rates because they provide an alternative reaction pathway that requires less energy than an uncatalyzed reaction. In contrast to some inorganic catalysts, most enzymes catalyze reactions at mild temperatures. In addition, enzymes are specific to the types of reactions they catalyze. Each type of enzyme has a unique, intricately shaped binding surface called an active site. Substrate binds to the enzyme s active site, which is a small cleft or crevice in a large protein molecule. In the lock-and-key model of enzyme action, the structures of the enzyme s active site and the substrate transition state are complementary. In the induced-fit model, the protein molecule is assumed to be flexible. 

Figure 14.24 The lock-and-key model for enzyme action. The correct substrate is recognized by its ability to fit the active site of the enzyme, forming the enzyme-substrate complex. After the reaction of the substrate is complete, the products separate from the enzyme. 

The lock-and-key model for enzyme action postulates that the stmctures of the enzyme and its substrate are complementary, such that the active site of the enzyme and the portion of the substrate molecule to be acted upon can fit together very closely. The structures of these portions of the molecules are unique to the particular enzyme-substrate pair, and they fit together much as a particular key is necessary to open a given lock. 

Living cells contain thousands of different kinds of catalysts, each of which is necessary to life. Many of these catalysts are proteins called enzymes, large molecules with a slotlike active site, where reaction takes place (Fig. 13.39). The substrate, the molecule on which the enzyme acts, fits into the slot as a key fits into a lock (Fig. 13.40). However, unlike an ordinary lock, a protein molecule distorts slightly as the substrate molecule approaches, and its ability to undergo the correct distortion also determines whether the key will fit. This refinement of the original lock-and-key model is known as the induced-fit mechanism of enzyme action. 

There are two main models of enzyme action. In the lock-and-key model, when the key (substrate) fits the lock (active site), the chemical change begins. However, experiments show that, in many cases, the enzyme changes shape when the substrate lands at its active site. Thus, rather than a rigidly shaped lock in which a particular key fits, the induced-fit model pictures a hand (substrate) entering a glove (active site), causing it to attain its functional shape. 

The specificity of the enzyme led to the postulate of a lock-and-key type of mechanism. The substrate molecule, by combining in a special way with the active site on the enzyme, is activated f or the reaction that it is to undergo. The active site on an enzyme may consist of more than one site on the protein molecule one site may attach to one part of the substrate molecule, while another site binds another part of the substrate molecule. The lock-and-key model seems to be generally correct, but the details of the action are different f or different enzymes. 

Using Analogies Explain why the model of enzyme action is called the lock-and-key model. 

An early theory of enzyme action, called the lock-and-key model, described the active site as having a rigid, inflexible shape. According to the lock-and-key model, the shape of the active site was analogous to a lock, and its substrate was the key that specifically fit that lock. However, this model was a static one that did not allow for the flexibility of the tertiary shape of an enzyme and the way we now know that the active site can adjust to the shape of a substrate. 

An understanding of enzyme action requires not only a knowledge of pathway and rates, but also an explanation of specificity. The dominant idea in this area was that of Emil Fischer, who described the enzyme-substrate complex in terms of lock and key (Fischer, 1894). In essence, Fischer presented a steric model where a cavity in the enzyme was assumed to be shaped to fit the substrate and to hold it firmly in place. This model served enzymologists well for decades and helped them to visualize the interactions between specific... 

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