Hemoglobin allosteric modulator

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]. 

FIGURE 6-29 Substrate-activity curves for representative allosteric enzymes. Three examples of complex responses of allosteric enzymes to their modulators, (a) The sigmoid curve of a homotropic enzyme, in which the substrate also serves as a positive (stimulatory) modulator, or activator. Note the resemblance to the oxygen-saturation curve of hemoglobin (see Fig. 5-12). (b) The effects of a positive modulator (+) and a negative modulator (—) on an allosteric enzyme in which K0 5 is altered without a change in Zmax. The central curve shows the substrate-activity relationship without a modulator, (c) A less common type of modulation, in which Vmax is altered and /C0.sis nearly constant. 

A similar system has been used to study the influence of allosteric interactions on cyanide dissociation in hemoglobin (112). The results of these RSSF studies demonstrate that the cyanide complex of the a- and 3-chains are spectroscopically distinguishable and that dissociation is a cooperative process that is modulated by allosteric effectors. 

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