Cooperativity allosteric proteins

There are exceptions to Michaelis-Menten behaviour. For example allosteric enzymes which instead of a hyperbolic curve in a Lversus [S] graph yield a sigmoidal plot (the behaviour is rather like non-catalytic allosteric proteins, such as haemoglobin, Section 2.5. This type of curve can indicate cooperative binding of the substrate to the enzyme. We have discussed cooperativity in Section 1.5 (see also Section 10.4.3). In addition, regulatory molecules can further alter the activity of allosteric enzymes. 

So how to explain the cooperative behaviour of allosteric proteins Need to explain both kinds of effects. 

Positive modulator or substrate in positive homotropic cooperativity) preferentially binds to the R form and maintains the allosteric protein in the, RR conformation. 

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. 

The key to allosteric behavior, including cooperativity and modifications of cooperativity, is the existence of multiple forms for the quaternary structures of allosteric proteins. The word allosteric is, derived from alio, other, and stetic, shape, referring to the fact that the possible conformations affect the behavior of the protein. The binding of substrates, inhibitors, and activators changes the quaternary structure of allosteric proteins, and the changes in structure are reflected in the behavior of those proteins. A substance that modifies the quaternary structure, and thus the behavior, of an allosteric protein by binding to it is called an allosteric effector. The term effector can apply to substrates, inhibitors, or activators. Several models for the behavior of allosteric enzymes have been proposed, and it is worthwhile to compare them. 

In 1965, Monod, Wyman, and Changeux proposed an important unified model for allosteric proteins (Monod et al, 1963 Monod et al, 1965). They have studied many examples of cooperative and aUosleric effects, and concluded that they were closely related and that conformational flexibility probably accounted for both phenomena. They have proposed a stmctural model for allosteric enzymes and proteins, which comprises the following postulates ... 

Identification of Hydrophobic Association with Rigor in Muscle and with the Tense, T-State, of Allosteric Proteins Exhibiting Positive Cooperativity... 

---