4.6:
Allosteric Regulation
Allosteric regulation is the control of an enzyme's activity through sites distinct from its active site.
When an effector molecule binds to such an allosteric site, it can induce a conformational change in the enzyme.
This change may increase the affinity of the enzyme's active sites for its substrates, enhancing the enzyme's activity— a process known as allosteric activation.
The reaction rates for many allosteric enzymes create a positive S-shaped curve when graphed against increasing substrate concentrations.
When a positive effector is added, the allosteric activation shifts the graph to a nearly hyperbolic curve.
On the other hand, if the binding of the effector causes a conformational change that decreases the affinity of the enzyme for its substrate, the process is referred to as allosteric inhibition.
This decrease in enzyme function can result in a reduced rate of the chemical reaction compared to the activated state.
4.6:
Allosteric Regulation
Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or synthesis of specific cellular molecules.
Allosteric Inhibition
In allosteric inhibition, the binding of an effector molecule to the allosteric site causes a conformational change that reduces the affinity of the enzyme for the substrate. Frequently, the allosteric inhibitor is a product of the enzyme or the enzyme pathway, allowing enzymatic products to limit their own production. This type of feedback inhibition prevents overproduction of products. As a classic example, isoleucine is an allosteric inhibitor of an enzyme important in its own synthesis.
Allosteric Activation
In contrast, an allosteric activator causes a conformational change that increases the affinity of the enzyme for its substrate. Allosteric activation dramatically increases the rate of reaction, as represented by the hyperbolic curve on a reaction rate versus substrate concentration graph. As an example, extracellular ligand binding to the transmembrane EGF receptor causes a conformational change that results in an increase in the intracellular kinase activity of the receptor. If an enzyme is composed of multiple subunits, binding of an allosteric activator to a single subunit can cause an increase in affinity and shape change for all of the affiliated subunits.
Suggested Reading
Suggested Reading
- Cornish‐Bowden, A. Understanding allosteric and cooperative interactions in enzymes. The FEBS Journal. 281 (2), 621-6332 (2014).
- Tsai, C.-J., Nussinov, R. Emerging allosteric mechanism of EGFR activation in physiological and pathological contexts. Biophysical Journal. 117 (1), 5-13 (2019).