Biochemistry - Chemical Reactions in Living Cells, Volume 1 - D. Metzler 1980

How molecules combine with each other
Cooperative conformational changes
Unequal substrate binding and induced fit

Let us assume that conformer B binds to X more tightly than conformer A (as illustrated in the diagram above, where the shapes of the binding sites of the two conformers differ). The true binding constants of conformers A and B with molecule X — denoted as K_AX and K_BX (or K_T and K_R) — are equal, respectively, to

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All equilibrium processes occurring in this system are presented below.

Note that the constant characterizing the equilibrium between AX and BX is a function of three other constants, namely K_tK_BX/K_AX. Now let us consider the following scenario. Suppose that in the absence of X, form A predominates, yet X binds much more strongly to B than to A. In this case, the equilibrium mixture will consist predominantly of either free A or BX (with smaller amounts of AX and B also present). This raises an interesting kinetic question: along which of the two possible pathways will the transition reaction from A to BX proceed [equation (44)]? The first option, assumed in the Monod–Wyman–Changeux model, posits that X binds exclusively to form B, a small amount of which is present in the mixture in equilibrium with A. According to the second option, X binds to A, after which AX rapidly converts into BX. In a sense, X induces a conformational change in protein A that facilitates "docking." This forms The basis of Koshland's concept, known as the induced-fit model. It should be borne in mind that knowing the equilibrium constants allows one to determine only the equilibrium concentrations of all four forms present in equation (4-44). However, when studying METABOLISM, we are usually more interested in reaction rates than in the state of equilibrium, and solely on the basis of equilibrium data, it is impossible to predict a priori which of the two possible pathways the reaction will actually follow.

Note that if the ratio K_BX/K_AX is very large, only a negligible amount of AX will be present in the equilibrium mixture. In this case, determining the value of K_AX experimentally is not feasible, but to describe The equilibrium state, knowing just two constants — K_T and K_BX — is sufficient.