Question

Which of the following assumptions Koshland did not make for his sequential model for allosteric enzyme interactions?

• A. The conformational change above can alter the substrate binding affinity of the other subunit.
• B. Once bound, a substrate elicits a conformational change in that subunit.
• C. Each enzyme subunit can have only two conformational states (R and T).
• D. One subunit may exist in R form, while the other has a T state at the same time.
• E. None of the above.

Answer 1

The correct option is E None of the above.

There are two popular models that explain the behavior of allosteric proteins/enzymes.

• The Concerted model explained by Monod, Wyman, and Changeux (WMC) and the Sequential model suggested by Koshland, Nemethy and Filmer (KNF). Both these models explain the non-hyperbolic kinetics by assuming that the allosteric behavior of enzymes is due to the interaction between the different subunits in an oligomer.
• Both the models proposed two distinct conformational states for the subunits as T (tense) and R (relaxed) which are in equilibrium. The binding affinities of ligand to these two conformations are different. According to the concerted model, as the substrate binds a single subunit of the oligomer, all the subunits change conformation from the inactive T conformation to the active R conformational the same time i.e a concerted change of conformation occurs. In the absence of a substrate, the enzyme exists mainly in the T form with small amounts of R form.
• The presence of substrate shifts the equilibrium to produce more of the R form. In contrast, the sequential model proposes that as ligand binds to one subunit, there is a change in conformation of the subunit which then induces a conformational change in a contiguous subunit.
• The effect of ligand binding is sequentially transmitted between the subunits. Unlike the concerted model, the sequential model can have tetramers that consist of both T and R states at the same time.
• Therefore, none of the options are correct