Homotropic interaction

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... 

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 kinetic cooperativity can be distinguished from the substrate binding cooperativity (spatial cooperativity by means of homotropic interactions) by means of binding studies, measurements of the initial speed and the determination of the type of conformation (9,12). 

The inhibition pattern of adenine is very complex and the inhibition constant is the sum of several effects. This probably involves a hybrid mechanism kinetic cooperativity and homotropic interactions. 

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

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. 

The glutamine-dependent CP synthase has been extensively purified in E. coli and shown to be a biotin-containing enzyme with marked allosteric properties [74,75]. Homotropic interaction is evident from the sigmoidal kinetics obtained with ATP as substrate. Negative effectors are UMP, UDP and UTP, and purine nucleotides, particularly IMP, act as positive effectors. 

The capacities for cooperativity and allosteric regulation elevate enzymes from the level of simple catalysts to that of the regulators of metabolism. In fact, cooperativity and allosteric regulation share a common mechanism—the alteration of the properties of the catalytic site by binding of a ligand to a second site on the enzyme. Cooperativity may be thought of as the homotropic interaction of identical catalytic sites, and allostery as the heterotropic interaction of a catalytic site and a dissimilar site which binds an allosteric modifier. 

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