Proteomics/Protein - Protein Interactions/Allosteric and Affinities

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« Protein Interactions
Allosteric Effects and Binding Affinities
Characterization of Binding Sites Determining Binding Experimentally

Page Edited and Updated by: Christopher Fucile

This Section:

Allosteric Effects and Binding Affinities[edit]

Allosteric binding occurs at an interface that is not within the active site of the protein, while allosteric regulation occurs through binding of an activator molecule in the interface of the allosteric site. Allosteric binding is cooperative, that is the affinity for the ligand of the molecule rises as the levels of ligand increase. Binding is said to be noncooperative if the concentrations of ligand have no effect on binding.[1]

There are two models for allosteric binding:

  • Concerted modeling
  • Sequential modeling.

Concerted Modeling:[edit]

In concerted modeling, the conformational changes of one protein subunit extend to all of the other subunits, such that all the subunits share the identical conformation. Without a ligand bound, the equilibrium of the conformation favors either a tensed or relaxed state, T or R. The conformation is shifted between these states depending on the binding of the ligand to an allosteric site.[2]

Sequential Modeling:[edit]

In sequential modeling the conformational changes of one protein subunit may induce similar changes in the others, but none of the subunits share identical conformations. Induced fit is an element of the sequential model. Collision with the interface elicits ligand conformational changes in such a way that there is relaxation in the subunit allowing the receptor to form fit around the ligand. But these conformational changes do not propagate to the surrounding subunits.[3]

Allosteric Inhibition occurs when the binding of a ligand in the manner decribed above decreases the binding affinity of substrates in the active site.

Binding Affinity[edit]

Receptor-Ligand binding can be characterized by the affinity, or attraction, the two have for each other. Binding sites with high affinity, have strong intermolecular forces between receptor-ligand and remain bound for longer periods of time than those of low affinity. High affinity sites have high molecule energies, and can transmit some of their energy to provide for conformational changes in the receptor. The concentration at which half amount of ligand is bound to the receptor is used to quantify binding affinities. High affinity sites have more ligand bound, whereas low affinity sites have less than half bound. Binding affinities are used to determine the number and location of binding sites present in a protein, and this information is gathered through computation of data determined through isothermal titration calorimetry and enzyme inhibition.[4]


1.^ Molecular Biology of the Cell, 4th Edition, < selected sections>

2.^ J. Monod, J. Wyman, J.P. Changeux. (1965). On the nature of allosteric transitions:A plausible model. J. Mol. Biol., May;12:88-118.

3.^ D.E. Jr Koshland, G. Némethy, D. Filmer (1966) Comparison of experimental binding data and theoretical models in proteins containing subunits. Biochemistry. Jan;5(1):365-8

4.^ "Binding Database" BindingDB. 30 March 2008 <>