Induced fitting

Fig. 2. Principle mechanisms of formation of a receptor—substrate complex (a) Fischer s rigid "lock-and-key" model (b) "induced fit" model showing...

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 7-5. Two-dimensional representation of Koshland s induced fit model of the active site of a lyase. Binding of the substrate A—B induces conformational changes In the enzyme that aligns catalytic residues which participate in catalysis and strains the bond between A and B, facilitating its cleavage.

C15-0139. According to the induced-fit model of enzyme activity, binding a reactant to the enz Tne causes a... 

C15-0141. In your own words, describe the induced-fit model of enz Tne specificity. Illustrate with diagrams, using a h q)othetical enz Tne that catalyzes the decomposition of a square but cannot catalyze the decomposition of a triangle ... 

I am surely not going to describe all of these complicated discussions which took place after the famous Monod-Wyman-Changeux paper, with the result that an increasing number of molecular states were introduced and that both kinds of processes, the induced-fit one, the concerted or... 

Another difficulty is that a peptide may be able to bind to an existing neutralizing monoclonal antibody by an induced-fit mechanism that is somehow driven by the pre-existing structure of the antibody paratope. However, the same induced-fit process may not take place when the peptide is used as the immunogen and is confronted in the host by a large population of B cell receptors allowing a variety of other interactions. 

Later on12, Koshland proposed the induced fit model of the active site action that considers that during the formation of the enzyme-substrate complex, the enzyme can change its conformation so as to wrap the substrate like it happens when a hand (substrate) fits in a globe (enzyme). This flexing puts the active site and bonds in the substrate under strain, which weakens the bonds and helps to lower the activation energy for the catalyzed reaction. 

Active Site Transition State Catalysis Lock and Key Induced Fit... 

What the induced-fit model is good at explaining is why bad substrates are bad, but like the lock and key model, it too fails to tell us exactly why good substrates are good. What is it about the proper arrangement that makes the chemistry fast ... 

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