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In biochemistry, an enzyme or other protein is allosteric if its activity or efficiency changes in response to the binding of an effector molecule at a so-called allosteric site. Changes that enhance activity are referred to as allosteric activation, while the opposite is called allosteric inhibition. "Allostery" is derived from the Greek "other site", referring to the typical scenario in which an enzyme's allosteric and active sites are distinct.
Models of allostery
Most allosteric effects can be explained by either the concerted (MWC) model put forth by Monod, Wyman, and Changeux, or by the sequential model described by Koshland, Nemethy, and Filmer. Both postulate that enzyme subunits exist in one of two conformations, tensed (T) or relaxed (R), and that relaxed subunits bind substrate more readily than those in the tense state. The two models differ most in their assumptions about subunit interaction.
The concerted model of allostery postulates that enzyme subunits are connected in such a way that a conformational change in one subunit is necessarily conferred to all other subunits. Thus all subunits must exist in the same conformation. The model further holds that in the absence of any ligand (substrate or otherwise), the equilibrium favors the T state over the R state. To summarize:
- all subunits must exist in the same conformation
- equilibrium favors the T state over the R state
The binding of substrate to one subunit causes all other subunits to assume the R state, thereby enhancing their affinity for substrate.
The sequential model of allostery holds that subunits are not connected in such a way that a conformational change in one induces a similar change in the others. Thus all enzyme subunits need not exist in the same conformation. Moreover, the sequential model dictates that molecules of substrate bind via an induced fit protocol. Namely, when a subunit randomly collides with a molecule of substrate, the active site essentially forms a glove around its substrate. While such an induced fit converts a subunit from the tensed to relaxed state, it does not propagate the conformational change to adjacent subunits. Instead, substrate binding at one subunit only slightly alters the structure of other subunits so that their binding sites are more receptive to substrate. To summarize:
- subunits need not exist in the same conformation
- molecules of substrate bind via induced fit protocol
- conformational changes are not propagated to all subunits
- substrate binding causes increased substrate affinity in adjacent subunits
Allosteric activation, such as the binding of oxygen molecules to haemoglobin, occurs when the binding of one ligand enhances the attraction between substrate molecules and other binding sites. With respect to hemoglobin, oxygen is effectively both the substrate and the effector. The allosteric, or "other," site is the active site of an adjoining protein subunit. The binding of oxygen to one subunit induces a conformational change in that subunit that interacts with the remaining active sites to enhance their oxygen affinity.
Allosteric inhibition occurs when the binding of one ligand decreases the affinity for substrate at other active sites. For example, when 2,3-BPG binds to a regulatory site on hemoglobin, the affinity for oxygen of all subunits decreases or increases.
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