Allosteric model

An Alternative Allosteric Model The Sequential Allosteric Model of Koshland, Nemethy, and Filmer... 

The allosteric model just presented is called a K system because the concentration of substrate giving half-maximal velocity, defined as -K0 5, changes in response to effectors (Figure 15.11). Note that Vjnax is constant in this system. 

Figure 10.24a and the allosteric model in Figure 10.24b. The circled data points were changed very slightly to cause an F-test to prefer either model for each respective model, illustrating the fallacy of relying on computer fitting of data and statistical tests to determine molecular mechanism. As discussed in Chapter 7, what is required to delineate orthosteric versus allosteric...

FIGURE 10.24 Simulation data set fit to an allosteric model (Equation 7.6 panel a) and to an orthosteric model (Equation 6.31 panel b). The data points circled with the dotted line were altered very slightly to cause the sum of squares for computer fit of the points to the model to favor either the allosteric or orthosteric model. It can be seen that very small differences can support either model even though they describe completely different molecular mechanisms of action. 

Rational design, 148-149, 152 Real-time assays, 83, 88 Receptor(s). See also Drug receptors affinity for, 6, 63 allosteric model of, 143 Clark s work, 3 classical model of, 44-45 concept of, 2-4 conformations, 13-14, 13 Of conservation equation for, 76 constitutive activity of, 49-51 coupling of, 27 definition of, 2 desensitization of, 34 efficacy for, 6... 

The simplest model that can describe allosteric interactions at GPCRs is the ternary complex allosteric model [9], As shown in Figure 1, according to this model two parameters define the actions of allosteric agent (X) its affinity for the unoccupied receptor (Kx) and its cooperativity (a) with the ligand (A) that interacts at the primary binding site a < 1 represents negative cooperativity a = 1, no cooperativity a > 1, positive cooperativity. 

Another example, and here Claude Debru will probably disagree with me, where co-operative phenomena have been given reductionistic explanation very, very successfully is the allosteric model, where, even though the model is complicated, which is a separate issue, it s purely mechanistic interactions that ultimately do give explanation. 

A. Goldbeter and R. Lefever, Dissipative structures for an allosteric model Application to glycolytic oscillations. Biophys. J. 12, 1302 1315 (1972). 

The 1963 allosteric model separate catalytic and regulator sites... 

To provide a mechanism for the feedback inhibition of these enzymes, the allosteric model was put forward in 1963. It was proposed that the enzyme that regulates the flux through a pathway has two distinct binding sites, the active site and a separate site to which the regulator binds. This was termed the allosteric site. The word allosteric means different shape , which in the context of this mechanism means a different shape from the substrate. The theory further proposed that when the regnlator binds to the allosteric site, it canses a conformational change in... 

Selected entries from Methods in Enzymology [vol, page(s)] Activation, 64, 177 concerted allosteric model, 64, 173 isotope exchange properties, 64, 10 negative cooperativity, 64, 189 rapid relaxation measurement, 64, 188, 189 sequential model, 64,... 

A subset in allosteric models of cooperativity. If an allosteric effector, upon binding to a cooperative enzyme, alters the Michaelis or dissociation constants (or [S0.5] value) for the substrate(s) (but not the h"max values), then that protein is a A system enzyme. See Monod-Wyman-Changeux Model K. E. Meet (1980) Meth. Enzymol. 64, 139. 

EXPONENTIAL BREAKDOWN SYMBOLIC COMPUTING Symmetry-conserving allosteric model, MONOD-WYMAN-CHANGEUX MODEL SYMPORT Symproportionation,... 

A typical chemical system is the oxidative decarboxylation of malonic acid catalyzed by cerium ions and bromine, the so-called Zhabotinsky reaction this reaction in a given domain leads to the evolution of sustained oscillations and chemical waves. Furthermore, these states have been observed in a number of enzyme systems. The simplest case is the reaction catalyzed by the enzyme peroxidase. The reaction kinetics display either steady states, bistability, or oscillations. A more complex system is the ubiquitous process of glycolysis catalyzed by a sequence of coordinated enzyme reactions. In a given domain the process readily exhibits continuous oscillations of chemical concentrations and fluxes, which can be recorded by spectroscopic and electrometric techniques. The source of the periodicity is the enzyme phosphofructokinase, which catalyzes the phosphorylation of fructose-6-phosphate by ATP, resulting in the formation of fructose-1,6 biphosphate and ADP. The overall activity of the octameric enzyme is described by an allosteric model with fructose-6-phosphate, ATP, and AMP as controlling ligands. 

I would like to comment on the theoretical analysis of two systems described by Professor Hess, in order to relate the phenomena discussed by Professor Prigogine to the nonequilibrium behavior of biochemical systems. The mechanism of instability in glycolysis is relatively simple, as it involves a limited number of variables. An allosteric model for the phosphofrucktokinase reaction (PFK) has been analyzed, based on the activation of the enzyme by a reaction product. There exists a parameter domain in which the stationary state of the system is unstable in these conditions, sustained oscillations of the limit cycle type arise. Theoretical... 

Fig. 6. A general allosteric model for the binding of substrate S to a four-subunit enzyme. The squares and circles represent different conformations of the subunits. The MWC model is shown by dashed lines and the AKNF model by dotted lines. The free substrate and arrows connecting the states are omitted for the sake of clarity.

The allosteric model for AMP inhibition of FDPase is supported by the results of experiments in which the enzyme is desensitized to the inhibitor with little or no loss of catalytic activity. Mild digestion with papain causes almost complete loss of AMP inhibition under conditions where the catalytic activity is only slightly decreased (13). Indeed the catalytic activity measured at alkaline pH has been observed to increase (36). 

Can the allosteric model account for differences between competitive and noncompetitive antagonists Explain why or why not. 

Bahr BA, Clarkson ED, Rogers GA, Noremberg K, Parsons SM (1992) A kinetic and allosteric model for the acetylcholine transporter-vesamicol receptor in synaptic vesicles. Biochemistry 31 5752-5762. 

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) ... 

H NMR findings that two-structure allosteric models are not sufficient to describe the cooperative oxygenation of Hb A. In this section, we shall summarize some of these results. 

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