The key difference between allosteric and covalent modulation is that allosteric modulation requires a phosphatase enzyme, whereas covalent modulation requires a kinase enzyme.
Modulation of an enzyme is a modification at the site in which a receptor or a ligand is going to bind with an enzyme. There are different types of modulations, and allosteric and covalent modulation are two of them.
CONTENTS
1. Overview and Key Difference
2. What is Allosteric Modulation
3. What is Covalent Modulation
4. Allosteric vs Covalent Modulation in Tabular Form
5. Summary – Allosteric vs Covalent Modulation
What is Allosteric Modulation?
Allosteric modulation is a term in pharmacology and biochemistry that refers to a group of substances that bind to a receptor to change that receptor’s response to the stimulus. Some of these modulators are drugs, e.g. benzodiazepines. Allosteric site is the site that an allosteric modulator binds to. It is not the same one to which the endogenous agonist of the receptor is going to bind (this particular site is named the orthosteric site). We can call both modulators and agonists as receptor ligands.
Moreover, there are three major types of allosteric modulators: positive, negative, and neutral modulations. The positive type can increase the response of the receptor by increasing the probability of the agonist binding with a receptor, by increasing the ability to activate the receptor (this is called efficacy), or by both these ways. On the other hand, the negative type can decrease agonist affinity and efficacy. Finally, the neutral type does not affect the agonist activity, but it can stop other modulators from binding to an allosteric site. Moreover, some allosteric modulators work as allosteric agonists.
Generally, allosteric modulators are able to alter the affinity and efficacy of other substances that act on a receptor. A modulator can also increase the affinity and lower efficacy or vice versa. Affinity is the ability of a substance to bind to a receptor. Efficacy, on the other hand, is the ability of a substance to activate a receptor that is given as a percentage of the ability of the substance to activate the receptor in comparison to the endogenous agonist of the receptor.
What is Covalent Modulation?
Covalent modulation is an important term used in biochemistry, and it refers to a group of substances that bind covalently to a receptor, changing its response. Enzymes are able to be regulated by the transfer of a molecule or atom from a donor to an amino acid side chain that can serve as the receptor of the transferred molecule. The other way of doing this is altering the amino acid sequence itself via proteolytic cleavage.
Covalent modulation involves the alteration of the shape and function of an enzyme via the covalent bonding of chemical groups to it. Moreover, this modulation is also known as post-translational modification. Usually, this modulation takes place in the endoplasmic reticulum and the Golgi apparatus. The sites that can often undergo post-translational modification are the sites having a functional group serving as a nucleophile in the reaction. These sites include hydroxyl groups of serine, threonine, and tyrosine, along with the amine forms of lysine, arginine, and histidine.
What is the Difference Between Allosteric and Covalent Modulation?
The key difference between allosteric and covalent modulation is that allosteric modulation requires a phosphatase enzyme, whereas covalent modulation requires a kinase enzyme.
The below infographic presents the differences between allosteric and covalent modulation in tabular form for side-by-side comparison.
Summary – Allosteric vs Covalent Modulation
Allosteric modulation refers to a group of substances that bind to a receptor to change that receptor’s response to a stimulus, while covalent modulation refers to a group of substances that bind covalently to a receptor and changes its response. The key difference between allosteric and covalent modulation is that allosteric modulation requires a phosphatase enzyme, whereas covalent modulation requires a kinase enzyme.
Reference:
1. “Covalent Allosteric Modulation.” London Lab, 25 June 2015.
Image Courtesy:
1. “AMPA receptor- Allosteric Modulation” By Ikenhower – Own work (CC BY-SA 4.0) via Commons Wikimedia
2. “Insulin path” By Uploaded by Fred the Oyster (CC BY-SA 4.0) via Commons Wikimedia