Hemoglobin ligand affinities

Fig. 32. Schematic representation of a hemoglobin molecule. Ligand binding changes the conformation of the ligated subunit, and might affect the ligand affinity of the neighboring subunits by different mechanisms...

The oxygen affinity of the derivative was shown to be about half that of unmodified hemoglobin under similar conditions, but a degree of cooperativity was preserved. Kquilihrium and kinetic ligand-binding studies on this derivative have been interpreted (62) to show a perturbed R state. It is beheved that although the reaction is between the two P-chains, aP-dimers function independentiy, probably through a flexible connection. 

Thermodynamically it would be expected that a ligand may not have identical affinity for both receptor conformations. This was an assumption in early formulations of conformational selection. For example, differential affinity for protein conformations was proposed for oxygen binding to hemoglobin [17] and for choline derivatives and nicotinic receptors [18]. Furthermore, assume that these conformations exist in an equilibrium defined by an allosteric constant L (defined as [Ra]/[R-i]) and that a ligand [A] has affinity for both conformations defined by equilibrium association constants Ka and aKa, respectively, for the inactive and active states ... 

The 3D structure of the 2,3-diphosphoglycerate (DPG) complex of hemoglobin (Hb) served to derive simple aromatic dialdehydes that mimic the function of DPG as an allosteric modulator of the oxygen affinity of Hb. Some of the resulting compounds were as active and even more active than DPG, the natural ligand [1-3]. 

It was pointed out in Section 6.8 that the term allosteric as coined by MCJ and MWC has been used with three different meanings. In Chapter 6 we discussed the allosteric effect in hemoglobin (Hb). There, the two allosteric sites were identical this has been referred to as the homotropic effect. When the two sites bind different ligands, the heterotropic effect, the induced fit by one ligand can either enhance or diminish the binding affinity of the second ligand (see the example in Section 4.5). 

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