Allosteric enzymes sequential model

Figure 10.16. Simple Sequential Model for a Tetrameric Allosteric Enzyme. The binding of a ligand (L) to a subunit changes the conformation of that particular subunit from the T (square) to the R (circle) form. This transition affects the affinity of the other subunits for the ligand.

Distinguishing between models. The graph below shows the fraction of an allosteric enzyme in the R state (f r) and the fraction of active sites bound to substrate (T) as a function of substrate concentration. Which model, the concerted or sequential, best explains these results ... 

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

Figure 4-50 The sequential interaction model of allosteric enzymes. As each site is occupied, the subunit carrying the site undergoes a change from the A conformation to the B conformation. As a result, new interactions between subunits are established and the affinities of the vacant sites change. K represents a dissociation constant. Thus, if the affinities of vacant sites increase, a, b, and c (the interaction factors) are <1 and we observe positive cooperativity (a sigmoidal velocity curve). The sequential interaction model also provides for, negative cooperativity (a, b, and c are > ). (o ) Dimer model. The two ways of arranging S to form a singly-occupied species is shown, (fe) Tetramer model. For simplicity, only one arrangement of each occupied species is shown.

Schematic diagram of conformational changes of. sequentially induced-fit model for a dimeric allosteric enzyme. The TT conformation is progressively converted to the RR conformation via the intermediate TR conformation through cooperative interaction in the presence of the positive modulator. In the presence of the negative modulator, the opposite conformational changes occur. In this model, the notion of. symmetry is discarded and the concept of induced fit is emphasized.

Two theoretical models that attempt to explain the behavior of allosteric enzymes are the concerted model and the sequential model. In the concerted (or symmetry) model, it is assumed that the enzyme exists in only two states T(aut) and R(elaxed). Substrates and activators bind more easily to the R conformation, whereas inhibitors favor the T conformation. The term concerted is applied to this model because the conformations of all the protein s protomers are believed to change simultaneously when the first effector binds. (This rapid concerted change in conformation maintains the protein s overall symmmetry.) The binding of an activator shifts the equilibrium in favor of the R form. An inhibitor shifts the equilibrium toward the T conformation. 

FIGURE 10.16 Simple sequential model for a tetrameric allosteric enzyme. The... 

F. 9.6. A sequential model for an allosteric enzyme. The sequential model is actually the preferred path from the Tq (taut, with 0 substrate bound) low-affinity conformation to the R4 (relaxed, with four substrate molecules bound) conformation, taken from an array of aU possible equilibrium conformations that differ by the conformation of only one subunit. The final result is a stepwise path in which intermediate conformations exist, and subunits may change conformations independently, depending on their geometric relationship to the subunits already containing bound substrate. 

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. 

Q Sequential model of cooperative binding of substrate S to an allosteric enzyme. Binding substrate to one subunit induces the other subunit to adopt the R state, which has a higher affinity for substrate. 

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

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

In the concerted model, all the subunits in an allosteric enzyme are found in the same form, either the T form or the R form. They are in equilibrium, with each enzyme having a characteristic ratio of the T/R. In the sequential model, the subunits change individually from T to R. 

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... 

What are the relative merits of the simple sequential model, the KNF model, and the MWC model Let us compare the rate equations for the tetrameric allosteric enzyme, derived with the aid of each model, and establish the differences (Table 4). 

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). 

Figure 11. Allosteric regulation A conformational change of the active site of an enzyme induced by reversible binding of an effector molecule (A). The model of Monod, Wyman, and Changeux (B) Cooperativity in the MWC is induced by a shift of the equilibrium between the T and R state upon binding of the receptor. Note that the sequential dissociation constants Kr and KR do not change. The T and R states of the enzyme differ in their catalytic properties for substrates. Both plots are adapted from Ref. 140. See color insert.

An allosteric dimer has an interaction factor, a, of 0.2 when analyzed according to the sequential interaction model (i.e., the binding of the first molecule of S increases the binding constant of the vacant site by a factor of 5—the dissociation constant of the vacant site decreases to 0.2 of the original value), (a) What is the relative distribution of enzyme species at [S] = 0.3 Ks (b) What is the specific velocity at [S] = 0.3 Ks (c) Will the calculated value of n,pp equal 2 ... 

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