Heterotropic 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. 

Metabolic activators and inhibitors are structurally dissimilar to substrates. These effectors exert regulatory control over catalysis by binding at an allosteric site quite distinct from the catalytic site. Such heterotropic interactions are mediated through conformational changes, often involving subunit interactions. Allosteric effectors can alter the catalytic rate by changing the apparent substrate affinity (K system) or by altering the... 

Heterotropic transition Heterotropic interactions may be transmitted to the regulatory sites by the tower helices and by changes at the subunit contacts. The simultaneous binding of allosteric activator and allosteric inhibitor gives rise to a structure intermediate between the T and the R structures. The heterotropic effect is exerted throughout the subunit interface contacts. 

Heterotropic interactions with multiple allosteric ligands... 

Let us now analyze the properties of the model with respect to heterotropic interactions between different aUosleric ligands. For this purpose, consider a system involving three stereospecific ligands, each binding at a different site. Assume that one of these ligands is the substrate (A) and, for the sake of simplicity, that it has significant affinity only for the sites in one of the two states... 

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. 

Ohe, M., Kajita, A. (1977) Studies on heterotropic interaction of hemoglobin. 1. Mass-spectrometric method for determination of p-kappaa of beta-146 histidine residue in human hemoglobin. Journal of Biochemistry, 81 (2), 431 34. 

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. 

---