The Concerted and Sequential Models for Allosteric Enzymes

The key to allosteric behavior, including cooperativity and modifications of cooperativity, is the existence of multiple forms for the quaternary structures of allosteric proteins. The word allosteric is, derived from alio, other, and stetic, shape, referring to the fact that the possible conformations affect the behavior of the protein. The binding of substrates, inhibitors, and activators changes the quaternary structure of allosteric proteins, and the changes in structure are reflected in the behavior of those proteins. A substance that modifies the quaternary structure, and thus the behavior, of an allosteric protein by binding to it is called an allosteric effector. The term effector can apply to substrates, inhibitors, or activators. Several models for the behavior of allosteric enzymes have been proposed, and it is worthwhile to compare them. 

Let us first define two terms. Homotropic effects are allosteric interactions that occur when several identical molecules are bound to a protein. The binding of substrate molecules to different sites on an enzyme, such as the binding of aspartate to ATGase, is an example of a homotropic effect. Heterotropic effects are allosteric interactions that occur when different substances (such as inhibitor and substrate) are bound to the protein. In the ATGase reaction, inhibition by GTP and activation by ATP are both heterotropic effects. 

Allosteric enzymes exhibit different behaviors compared to nonallosteric enzymes, and the Michaelis-Menten equations are not applicable. 

A plot of velocity versus [S] for an allosteric enzyme has a sigmoidal shape. One type of control often seen with allosteric enzymes is called feedback inhibition. 

Inhibitors and activators can control the activity of an allosteric enzyme. 

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Recall Distinguish between the concerted and sequential models for the behavior of allosteric enzymes. 

Two major models for allosteric enzymes have been proposed. These are the sequential interaction model and the concerted-symmetry ... 

The two principal models for allosteric enzyme behavior are called the concerted model and the sequential model. 

The two principal models for the behavior of allosteric enzymes are the concerted model and the sequential model. They were proposed in 1965 and 1966, respectively, and both are currently used as a basis for interpreting experimental results. The concerted model has the advantage of comparative simplicity, and it describes the behavior of some enzyme systems very well. 

The concerted symmetry model is much more versatile than simple sequential models described by Adair or Hill. This model is endowed by the variable values of Kr, L, and c, and therefore may provide explanations for many properties of allosteric enzymes and proteins, including... 

The MWC concerted-symmetry and KNF sequential interaction models may be considered as extreme cases of the more general model shown in Fig. 19. A general model for a four-site allosteric enzyme involves the hybrid oligomers. The first and the fourth column in Fig. 19 represent the concerted-symmetry model. The diagonal represents the sequential interaction model. As shown, there are 25 different types of enzyme forms. If the potential nonequivalent complexes are included (such as, e.g., two different T3RS2), the number raises to 44 possible enzyme forms (Hammes Wu, 1971). 

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