Enzyme sequential model

A model used to explain cooperativity on the basis of ligand-induced changes in conformation that may or may not alter the subunit-subunit interfaces of oligomeric enzymes and receptors. This model has also been referred to as the Adair-Koshland-Nemethy-Filmer model (AKNF model), the induced-fit model, and the sequential model. 

Two major models are typically used to describe these situations the concerted model and the sequential model. In the concerted model, the enzyme has two major conformations a relaxed form that can bind the appropriate reactant molecule(s) and a tight form that is unable to tightly bind the reactant molecule(s). In this model, all subunits containing reactive sites change at the same time (Figure 16.7). An equilibrium exists between the active and inactive structures. Binding at one of the sites shifts the equilibrium to favor the active relaxed form. 

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.

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. 

Earlier writers have also expressed useful views about proper characteristics of model reactions. In particular, Kosower, in a work that broke new ground in chemical biology ([5], pp. 276-277), suggested the difficulty of achieving the duplication of enzyme mechanisms with model compounds but noted that mechanistic parallels between enzyme and model reactions can nevertheless lead to informative results, culminating in what he denoted congruency between enzyme and model reactions, i.e., a very strong resemblance in terms of reactant structures and of the nature and sequential order of mechanistic events. 

More detailed analysis of the difference between symmetry and sequential models could be found in specialized literature (V.Leskovac, Comprehensive enzyme kinetics, Kluwer Academic/Plenum publishers, New York, 2003). 

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. 

The sequential model sacrifices a certain amount of simplicity for a more realistic picture of the structure and behavior of proteins it also deals very well with the behavior of some enzyme systems. 

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. 

In the sequential model, subunits of the enzyme can change sequentially from the T form to the R form and back again. 

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). 

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