In pharmacy and biochemistry, allosteric modulator refers to a substance that directly influences or modulates effects of an inverse agonist or agonist at the target protein such as receptor. The role of allosteric modulator is to bind a suit that is distinct from one that is from the binding site of orthosteric agonist.
Usually, allosteric modulators induce confrontational change in the structure of the protein. Positive allosteric modulator, also known as allosteric enhancer is the main substance that induces the amplification of agonists’ effect. On the other hand, negative modulator reduces effects of orthosteric ligand. However, it is not active when orthosteric ligand is absence.
The substances occupying the site of the allosteric binding are functionally neutral and are called the silent allosteric modulators. Classic benzodiazepines are called positive allosteric modulators. Modulatory activity may be of the first order or of the second order or even both. Second-order modulator alters madulatory activity of the first-order modulators. An example of a second-order modulator is a –Epigallocatechine-3-gallate at the GABAA receptors.
Allosteric agonists are distinguished from modulators. They are usually defined as the ligands that are capable of directly activating receptor by biding to the site of a receptor that is distinct from a primary site or orthosteric, the allosteric site. Usually, they compete to occupy the allosteric receptor. They can also bind even when orthosteric ligand is absent. This is different from allosteric modulator because it produces effect directly where just like a modulator it induce indirect effect. This implies that they do not have direct effect on their own. The ago-allosteric modulators are allosteric modulators and allosteric agonists.
Ago-allosteric modulator acts just like endogenoust agonists enhancer and as an agonist. It increases the potency of agonist, with dose ranging over the response that is to be produced as well as providing superagonism. Superagonism occurs when efficacy is more than 100 percent. The ago-allosteric modulator can be negative, positive or neutral. Efficacy is increased by neutral ago-allosteric modulator although they do not affect potency. Negative ago-allosteric modulators affect potency negatively while causing positive effect on agonist efficacy. Positive ago-allosteric modulators increase both potency and efficacy.
Allosteric modulators and allosteric modulation is always recognized as the widespread and general mechanism that is used in controlling the function of protein. This is because by binding to regulatory sites that are different from active site on protein, modulators cause confrontational change that can have profound influence on the function of protein.
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Originally posted 2015-12-01 06:15:18.
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