The symmetry model

For example, if two atoms that are related by a plane of mirror symmetry move onto that plane, they fuse to become a single atom. Thus atoms that lie on elements of symmetry (special positions) will occur less frequently in the building block than ones that lie on positions with no symmetry. The higher the 

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Various models have been offered to describe the mechanisms of allosteric regulation of enzyme activty, of which the symmetry model (Monod et al., 1965) is the simplest. The symmetry model has proven suitable in many cases to explain the experimentally observed characteristics of allosteric enzyme regulation. 

The symmetry model (fig. 2.4) of allostery can describe the cooperative binding of substrate to enzyme (homotropic effect), as well as the influence of effector molecules on the activity of enzymes (heterotropic effect). 

Fig. 2.4. The symmetry model of allostery. Shown here is the succesive binding of a hgand L to a protomer of a tetrameric protein with four ligand-binding sites according to the symmetry model. T tense form, R relaxed form.

The influence of effector molecules is described by the symmetry model in the following manner ... 

Two different enzymatically active forms of PFK could be identified which may be considered the R and T form in the framework of the symmetry model. The R form possesses a high affinity for the substrate fructose-6-P, the T form binds fructose-6-P with lower affinity. Upon binding of the inhibitor phosphoenolpyruvate, PFK converts to the T form. The enzyme is foimd in the R form upon binding the substrates (ATP or fructose-6-P) or the activator (ADP). There exist high resolution crystal structures of both forms. 

In the framework of the symmetry model (see 2.3), a T- and R-form can be formulated for glycogen phosphorylase. In the T-form glycogen phosphorylase binds its substrates and activating effectors with lower affinity, while in the R-form it possesses higher affinity for substrates and activating effectors. 

Alternative models for hemoglobin allostery, (a) In the symmetry model hemoglobin can exist in only two states. (b) In the sequential model hemoglobin can exist in a number of different states. Only the subunit binding oxygen must be in the high-affinity form. 

Allosteric Enzymes Typically Exhibit a Sigmoidal Dependence on Substrate Concentration The Symmetry Model Provides a Useful Framework for Relating Conformational Transitions to Allosteric Activation or Inhibition Phosphofructokinase Allosteric Control of Glycolysis Is Consistent with the Symmetry Model Aspartate Carbamoyl Transferase Allosteric Control of Pyrimidine Biosynthesis Glycogen Phosphorylase Combined Control by Allosteric Effectors and Phosphorylation... 

The Symmetry Model Provides a Useful Framework for Relating Conformational Transitions to Allosteric Activation or Inhibition... 

Using the symmetry model, the fraction of the binding sites occupied at any given substrate concentration can be described with an expression that includes the substrate dissociation constants for the two conformations (KR and Kr) and the equilibrium constant between the T and R conformations in the absence of substrate, L = [T]/[R], Thus, the symmetry model attempts to explain the difference between Kx and K2 in equation (3) by introducing a third independent parameter. Considering that equation (3) can fit the experimental data for a dimeric enzyme with only two pa-... 

The symmetry model is useful even if it does oversimplify the situation, because it provides a conceptual framework for discussing the relationships between conformational transitions and the effects of allosteric activators and inhibitors. In the following sections we consider three oligomeric enzymes that are under metabolic control and see that substrates and allosteric effectors do tend to stabilize each of these enzymes in one or the other of two distinctly different conformations. 

Phosphofructokinase Allosteric Control of Glycolysis Is Consistent with the Symmetry Model... 

Phosphofructokinase was one of the first enzymes to which Monod and his colleagues applied the symmetry model of allosteric transitions. It contains four identical subunits, each of which has both an active site and an allosteric site. The cooperativity of the kinetics suggests that the enzyme can adopt two different conformations (T and R) that have similar affinities for ATP but differ in their affinity for fructose-6-phosphate. The binding for fructose-6-phosphate is calculated to be about 2,000 times tighter in the R conformation than in T. When fructose-6-phosphate binds to any one of the subunits, it appears to cause all four subunits to flip from the T conformation to the R conformation, just as the symmetry model specifies. The allosteric effectors ADP, GDP, and phosphoenolpyruvate do not alter the maximum rate of the reaction but change the dependence of the rate on the fructose-6-phosphate concentration in a manner suggesting that they change the equilibrium constant (L) between the T and R conformations. 

The symmetry model of Monond, Wyman, and Changeux (Monad et al., 1965). This model was originally termed the allosteric model. The model is based on three postulates about the structure of an oligomeric protein (allosteric protein) capable of binding ligands (allosteric effectors) ... 

The symmetry model of Monad, Wyman and Changeux (Monad et al, 1965) ... 

Classical models for the cooperative binding to oligomeric proteins, which are formally applicable also for synthetic receptors, include the symmetry model of... 

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