Homotropic allosteric interaction

According to the concerted model, an allosteric activator shifts the conformational equilibrium of all subunits toward the R state, whereas an allosteric inhibitor shifts it toward the T state. Thus, ATP (an allosteric activator) shifted the equilibrium to the R form, resulting in an absorption change similar to that obtained when substrate is bound. CTP had a different effect. Hence, this allosteric inhibitor shifted the equilibrium to theT form. Thus, the concerted model accounts for the ATP-induced and CTP-induced (heterotropic), as well as for the substrate-induced (homotropic), allosteric interactions of ATGase. 

Outline the effects of heterotropic and homotropic allosteric interactions on the equilibrium between the T and R forms of ATCase. 

When binding of a substrate molecule at an enzyme active site promotes substrate binding at other sites, this is called positive homotropic behavior (one of the allosteric interactions). When this co-operative phenomenon is caused by a compound other than the substrate, the behavior is designated as a positive heterotropic response. Equation (6) explains some of the profile of rate constant vs. detergent concentration. Thus, Piszkiewicz claims that micelle-catalyzed reactions can be conceived as models of allosteric enzymes. A major factor which causes the different kinetic behavior [i.e. (4) vs. (5)] will be the hydrophobic nature of substrate. If a substrate molecule does not perturb the micellar structure extensively, the classical formulation of (4) is derived. On the other hand, the allosteric kinetics of (5) will be found if a hydrophobic substrate molecule can induce micellization. 

Heme—chemical models 307 Hemoglobin 289, 304-307 allosteric interactions 289-292, 302 Henderson-Hasselbalch equation 170 Heterotropic 290 Hexokinase 23, 51, 364 Hill constant 299, 300-302, 304 Hill equation 297 - 300 Hinge motions 48 HIV protease 486 Holoe nzyme 458 Homology 8, 9 Homology modeling 537 Homotropic 290 Hpr (histidine-containing... 

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. 

The chart in Fig. 2 shows an alternate path for the formation of dUMP by direct deamination of dCMP. This may be how cytidine could be converted to thymidylate in the cases cited above [125,126]. However, this deaminase is not usually detected in E. coli but is induced by infection with T(even) phages [132,133]. It has also been purified from chick embryo and mammalian tissues, and its properties have been extensively analyzed [134-136]. It acts as a typical allosteric enzyme in both the phage-infected E. coli and animal systems. Homotropic substrate interaction is evident, and this is modified by dCTP as an activator, and by dTTP (sometimes dGMP) as an allosteric inhibitor. This type of control apparently functions to regulate the level of dTTP by feedback inhibition and by activation when the supply of dTTP is depleted. Cytidine deaminase (EC 3.5.4.5) isolated from sheep liver [137] appears to have the same allosteric properties, with the same positive and negative effectors, as those of dCMP deaminase. The latter enzyme is also induced by phage infection in B. subtiUs, and in contrast to the deaminase from all other sources it does not show allosteric inhibition or activation by any nucleotide [138]. 

Homotropic allosteric effect appears in the system with identical ligands, and heterotropic allosteric effect is manifested for interaction between different ligands. 

Allosteric binding occurs when two molecules bind to different sites on the target. When the two molecules are identical, it is termed homotropic interaction. If the molecules differ from each other, it is termed heterotropic interaction. Binding is competitive when two different ligand molecules compete for the same site. We discuss ligand binding further in Chapter 3. The specificity of ligand-receptor interaction is illustrated in Exhibit 2.9. 

STEREOCHEMICAL TERMINOLOGY, lUPAC RECOMMENDATIONS HOMOTROPIC INTERACTION MONOD-WYMAN-CHANGEUX MODEL ALLOSTERISM HEMOGLOBIN "HONDO,"... 

The enzyme from B. stearothermophilus is an a4 tetramer of subunit Mr 33 900. Early kinetic studies indicated that the enzyme acts in a manner that is qualitatively consistent with an MWC two-state model. The enzyme acts as a A system i.e., both states have the same value of kcal but different affinities for the principle substrate. In the absence of ligands, the enzyme exists in the T state that binds fructose 6-phosphate more poorly than does the R state. In the absence of ADP, the binding of fructose 6-phosphate is highly cooperative, and h = 3.8. The positive homotropic interactions are lowered on the addition of the allosteric effector ADP, with h dropping to 1.4 at 0.8-mM ADP.52 ADP thus binds preferentially to the R state. The allosteric inhibitor phosphoenolpyruvate binds preferentially to the T... 

Fushinobu, S., Ohta, T., and Matsuzawa, H. (1998). Homotropic activation via the subunit interaction and allosteric symmetry revealed on analysis of hybrid enzymes of L-lactate dehydrogenase./. Biol. Chem., 273, 2971-2976. 

Homotropic this is where the sites are identical, and each sites is allosteric to the others. This is like the cooperative interactions seen in oxygen binding by haemoglobin - four (essentially) identical oxygen binding sites interacting with each other allosterically. 

The allosteric kinetic effects of ATCase are shown in Figure 7-6. The interaction of substrates with the enzyme is cooperative (an example of homotropic cooperativity), as indicated by the sigmoidal shapes of the v versus [S] plots, CTP being an inhibitor and ATP an activator. These modulators compete for the same regulatory site and modulate the affinity of the enzyme for its... 

Identifying the region of the molecule involved in the direct transmission of allosteric effects is clearly important for understanding how allosteric transitions might be manipulated for therapeutic purposes, particularly if one wished to block an allosteric transition. Understanding the structure-function relationships of the ligands binding to their various sites in an allosteric protein is also critically important. For a homotropic interaction... 

The expression is identical to that for the homotropic interactions, except that L is replaced by an apparent allosteric constant L, defined as ... 

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