Allosterism haemoglobin

Bettati S et al Allosteric mechanism of haemoglobin Rupture of salt-bridges raises the oxygen affinity of the T-structure. J Mol Biol 1998 281 581. 

Not all allosteric proteins are enzymes. In fact, probably the best-known and characterized allosteric protein is haemoglobin, which like an enzyme binds ligands (small molecules) to itself, for example, oxygen rather than a substrate. 

Haemoglobin is one of the most well studied and best understood proteins thanks largely to the early work of Max Perutz, John Kendrew and colleagues. Haemoglobin is now often used as a model allosteric protein and to illustrate the impact of protein structural alterations in disease. 

Although haemoglobin is not a catalytic protein, it shares important features in common with enzymes, for example ligand binding, allosterism and inhibition . Before continuing, the reader should ensure familiarity with the concepts of allosterism as described in Section 3.2. 

K. Imai, Allosteric effects in haemoglobin. Cambridge Univ. Press, London and New York, 1982. 

Imai, K., 1982, Allosteric Effects in Haemoglobin, Cambridge University Press, London. 

There are two types of control shown by allosteric enzymes. They can be modulated by a molecule other than a substrate of the enzyme (termed heterotrophic enzymes, e.g. threonine dehydratase), or by the substrate itself (termed homotrophic enzymes, e.g. oxygen binding to haemoglobin). They contain two or more binding sites for the substrate, and activity is modulated by the number of binding sites which are filled. 

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. 

Homotropic this is where the sites are identical, and each sites is allosteric to the others. This is like the cooperative interactions seen in oxygen binding by haemoglobin - four (essentially) identical oxygen binding sites interacting with each other allosterically. 

Fig. 6.3. Monod-Wyman-Changeux model for haemoglobin as an allosteric protein. R (relaxed) subunits are shown as circles, and the T (tense) subunits as squares. The filled circles and squares indicate oxygen binding. With increased oxygen saturation, the proportion of R subunits increases...

Brittain, T. (1991). Cooparativity and allosteric regulation in non-mammalian vertebrate haemoglobins. Comp. Biochem. Physiol, 99B, 731-40. 

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