Hemoglobin allosteric protein

For many years hemoglobin was the only allosteric protein whose stereochemical mechanism was understood in detail. However, more recently detailed structural information has been obtained for both the R and the T states of several enzymes as well as one genetic repressor system, the trp-repressor, described in Chapter 8. We will here examine the structural differences between the R and the T states of a key enzyme in the glycolytic pathway, phosphofructokinase. 

The properties of individual hemoglobins are consequences of their quaternary as well as of their secondary and tertiary structures. The quaternary structure of hemoglobin confers striking additional properties, absent from monomeric myoglobin, which adapts it to its unique biologic roles. The allosteric (Gk alios other, steros space ) properties of hemoglobin provide, in addition, a model for understanding other allosteric proteins (see Chapter 11). 

On the other hand, small start-up companies focused intensely and entirely on what they were created to do, with the incentive that early and even later employees would be well rewarded if the venture was successful. It was clear to me, in this case, that if the translation from basic and preclinical research to clinical trials were to occur, our best chance was to initiate a company. For the most part, big pharmaceutical houses have stayed clear of allosteric effectors as drugs. We had the enormous advantage that far more is known about hemoglobin as an allosteric protein than any other. 

Alternative Theories on How Hemoglobins and Other Allosteric Proteins Work Muscle Is an Aggregate of Proteins Involved in Contraction... 

Two quite different models were proposed about 25 years ago to explain the unusual nature of the hemoglobin oxygen-binding curve (fig. 5.14). These models can also be used as a starting point for discussing other allosteric proteins. The first model, introduced by Jacque Monod, Jeffery Wyman, and Pierre Changeux in 1965, is called the symme-... 

Allostery Hemoglobin is an allosteric protein. This means that the binding of 02 to one... 

Fig. 2.3 Ligand binding to allosteric and non-allosteric proteins oxygen bindig to myoglobin and hemoglobin, a) the...

It should be emphasized that the concerted and sequential models are theoretical models, that is, the behavior of many allosteric proteins appears to be more complex than can be accounted for by either model. For example, the cooperative binding of Oz by hemoglobin (the most thoroughly researched allosteric protein) appears to exhibit features of both models. The binding of the first 02 initiates a concerted T — R transition that involves small changes in the conformation of each subunit (a feature of the sequential model). In addition, hemoglobin species with only one or two bound 02 have been observed. 

Thus, hemoglobin obeys neither the KNF nor the MWC model completely but follows a novel path containing features of both models. This more recent model does not mean that the earlier models are generally incorrect. Allosteric proteins exist that appear to follow the MWC model almost exactly. 

A classic illustration of the quaternary structure and its effect on protein properties is a comparison of hemoglobin, an allosteric protein, with myoglobin, which consists of a single polypeptide chain. 

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