Homotropic interactions models

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... 

This equation expresses the second fundamental property of the MWC model, namely, that the heterotropic effect of an allosteric ligand upon the saturation function for another allosteric ligand should be to modify the homotropic interaction of the latter. 

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... 

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. 

Fig. is. Model for the mechanism of homotropic cooperativity in aspartate transcarbamylase. Shown schematically are the two extreme conformations in the T state and the R state. The binding of the substrates at one active site induces the domain closure in that catalytic chain and requires a quaternary conformational change which allows the 240s loops of the upper and lower catalytic chains to move to their final positions. The formation of the R state, in a concerted fashion, is further stabilized by a variety of new interactions as shown. [Reprinted with permission from Ref. (/).]... 

The model, therefore, accounts for both homotropic and heterotropic interactions and for their interdependence. No particular assumptions has been, or need be, made about the strncmre of the specific sites or about the stmcture of the protein, except that it is a symmetrically bonded oligomer, the symmetry of which is conserved when it undergoes a transition from one to another state. 

Nierengarten et al. reported liquid crystalline pillar[5]- and pillar[6]ar-enes. They synthesized pillar[5]arene 6.32 and pillar[6]arene 6.33 with 10 and 12 mesogenic cyanobiphenyl units, respectively (Figure 6.20). Both compounds showed smectic A phase (focal-conic fan texture and homotropic areas) over a broader temperature range when compared with the model compound. This can be explained as the macrocyclic effect Inter-molecular 71-71 interactions between neighboring pillar[n]arene cores stabilized the smectic A phase. 

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