Enzyme, "lock-and-key

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. 

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. 

Early in the last century, Emil Fischer compared the highly specific fit between enzymes and their substrates to that of a lock and its key. While the lock and key model accounted for the exquisite specificity of enzyme-substrate interactions, the imphed rigidity of the... 

In terms of the carbanion equivalent, the enolase superfamily has a strong relation with decarboxylation reaction. This family is characteristic in its promiscuity. If one is reminded of the phrase lock and key theory for the relation between the substrate and the enzyme, the word promiscuity of the enzyme may be unbelievable. However, in addition to natural promiscuity, we can change the enzyme to be promiscuous by introducing mutation, especially in the case of the enolase superfamily. This will be one of the challenging problems in future. For that purpose, biotechnology and informatics skill will be essential tool in addition to precise analysis of the reaction mechanism. 

The binding of a substrate to its active center was first postulated by E. Fisher in 1894 using the lock and key mechanism which states that the enzyme interacts with its substrate like a lock and a key, respectively, i.e. the substrate has a matching shape to fit into the active site. This theory assumed that the structure of the catalyst was completely rigid and could not explain why the macromolecule was able to catalyze reactions involving large substrates and not those with small ones, or why they could convert non natural compounds with different structural properties to the substrate. 

The LOCK AND KEY model for enzyme specificity uses complementarity between the enzyme active site (the lock) and the substrate (the key). Simply, the substrate must fit correctly into the active site—it must be the right size and shape, have charges in the correct place, have the right hydrogen-bond donors and acceptors, and have just the right hydrophobic patches. 

HOW EMIL FISCHER WAS LED TO THE LOCK AND KEY CONCEPT FOR ENZYME SPECIFICITY1... 

At this point Fischer concluded that the enzymes, in terms of the configurations of the substrates, are as fastidious as yeast and other organisms. He then returned to the above-mentioned hypothesis that he and Thierfelder had proposed (30) and concluded (32) that the protein substances known as invertin and emulsin, like the substrates whose hydrolyses they effected, were asymmetrically formed molecules. On the basis of this consideration, he came to the momentous lock and key concept for enzyme activity and commented as follows ... 

To use a picture, / would like to say that enzyme andglucoside have to fit to each other like a lock and key in order to exert a chemical effect on each other. 

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