A ligand is a small molecule that is able to bind to proteins by weak interactions such as ionic bonds, hydrogen bonds, Van der Waals interactions, and hydrophobic effects. In some cases, a ligand also serves as a signal triggering molecule. A ligand can be a substrate inhibitor, activator or a neurotransmitter.
For example, oxygen is the ligand that binds to both hemoglobin and myoglobin.
Binding site: a region of the protein that is complementary to a specific molecule or ion. This site usually exhibits specificity to ligands. The weak interactions of the primary structure of protein, specifically the side chains to the ligand, usually initiates a response. The concentration at which all binding sites are bound to a ligand is termed the point of saturation.
Induced fit is the concept that an enzyme is a flexible rather than a rigid entity. Interactions between the active site and substrate continually reshape the tertiary structure slightly. Instead of the substrate simply binding to the active site, the enzyme and substrate mold to induce a fit similar to that of a lock and key. This allows the substrate to be in the precise position to enable a catalytic response.
Dissociation constant: Kd is the tendency for a ligand to bind to a binding site. It is measured by the ratio of concentrations of the ligand and enzyme over the concentration of the Enzyme-ligand complex. It is equal to the concentration of the ligand at which the total binding sites are half occupied. Association constant is equal to the reciprocal of the dissociation constant.
Cooperativity: Allosterism: Hill equation:
A molecule, atom, or ion that is charged or neutral and of non-bonding pairs of electrons as electron donors or Lewis bases that form bond to a central metal atom or ion to be as complex ion; it is important for control of chemical reactivity of the complex of ligands and metal; monofunctional ligands are complex ions that have one non-bonding pair of electrons, polyfunctional or known as chelates, two or more. Biological ligands are mostly electron-donating groups; important one of biological system is heme that is of nitrogen donating groups and forms chelate structure.
When a ligand binds to the protein, the chemical conformation of the protein changes. The tertiary structure of the protein is altered. The conformation of the protein determines the function of the protein, as structure often denotes a lot about the function. The tendency in which the ligand binds to the protein is known as the term affinity.
The binding affinity depends on the interaction of the binding site with the ligand. When the interaction of the intermolecular forces between the ligand and binding site are high, the affinity is increased. Similarly, when the intermolecular forces between the ligand and binding site are weak, the affinity is low.
When the affinity is high for the ligand binding, the concentration of the ligand does not need to be high in order for the ligand to bind to its maximum potential. Similarly, when the affinity is low, the concentration of the ligand must be large in order for the ligand to bind properly to the binding site.
For example, ligands have an effect on biphosphoglycerate in the T-form of hemoglobin. The ligand binds to the deoxyhemoglobin cavity which decreases the oxygen affinity. Thus, it stabalizes the deoxy form of hemoglobin.
A ligand is a substance that has the ability to bind to and form complexes with other biomolecules in order to perform biological processes. Essentially, it is a molecule that triggers signals and binds to the active site of a protein through intermolecular forces (ionic bonds, hydrogen bonds, Van der Waals forces). The docking (association) is usually a reversible reaction (dissociation). Within biological systems, it is rare to find irreversible covalent bonds between the ligand and its target molecule. The chemical conformation is changed when the ligand bonds to its receptors. For example, the three dimensional shape of the receptor protein is change upon the binding of the ligand. Also, the conformational state of a receptor protein will cause variations in the functional state of a receptor. The strength/tendency of the ligand binding is known as affinity. Different types of ligands include substrates, inhibitors, activators, and neurotransmitters.
Receptor/Ligand Binding AffinityEdit
Human cells use receptor-mediated endocytosis to take in cholesterol for use in the synthesis of membranes and as a precursor for the synthesis of other steroids. Cholesterol travels in the blood in particles called low-density lipoproteins(LDLs), complexes of lipids and proteins. These particles act as ligands hence they bind to LDL receptors on membranes and enter the cells by endocytosis. In humans with familial hypercholesterolemia, an inherited disease characterized by a very high level of cholesterol in the blood, the LDL receptor proteins are defective or missing so the LDL particles cannot enter cells. Instead, cholesterol accumulates in the blood, where it contributes to early atherosclerosis. Atherosclerosis is the buildup of lipid deposits within the walls of blood vessels, causing of the bulge inwards of vessels and impeding blood flow.
Note: These are the three types of endocytosis that the cell participates in. The third one represents the receptor-ligand binding mentioned for cholesterol in humans.
How Ligands BindEdit
The binding of a ligand to a protein is greatly affected by the structure of the protein and is often accompanied by conformational changes. As an example, the specificity with which heme binds its various ligands changes when the heme is a component of myoglobin. When carbon monoxide binds to free heme molecules, it binds more than 20,000 times better than oxygen does, but it only binds 200 times better than oxygen when the heme is bound in myoglobin. The difference is most likely due to steric hindrance but there are other factors that have not yet been well-defined that may also affect the interaction of heme with carbon monoxide.
Reversible Binding of Protein to LigandEdit
Oxygen is poorly soluble in aqueous solutions and cannot be carried to tissues in sufficient quantity if it is only dissolved in blood serum. The diffusion of oxygen through tissues is also ineffective over distances greater than a couple of millimeters. The evolution of larger, multicelluluar animals, though, depended on the evolution of proteins that could transport and store oxygen, but none of the amino acid side chains in proteins are suited for the reversible binding of oxygen molecules. This function was filled by certain transition metals, among them being iron and copper, that have a strong tendency to bind oxygen. The multicellular organisms make use of the properties of metals, most commonly iron, for oxygen transport. However, iron promotes the formation of highly reactive oxygen species that can damage DNA and other macromolecules. Therefore, the iron used in cells is bound in forms that isolate it or make it less reactive. In order for multicellular organisms to make use of iron, especially when it must be transported over long distances, iron is incorporated into a protein-bound prosthetic group called heme. Iron in the ferrous state binds oxygen reversibly while the ferric state does not bind oxygen. Heme is found in many oxygen-transporting proteins as well as in proteins that participate in oxidation-reduction reactions. When oxygen binds to heme, the electronic properties of the heme iron change, which accounts for the change in color from the dark purple of oxygen-depleted venous blood to the bright red of oxygen-rich arterial blood. Some small molecules, such as carbon monoxide (CO) and nitrogen monoxide (NO), coordinate to heme iron with greater affinity than does oxygen gas. When a molecule of carbon monoxide is bound to heme, oxygen is excluded and this is why carbon monoxide is highly toxic to aerobic organisms. By surrounding and isolating heme, oxygen-binding proteins can regulate the access of CO and other small molecules to the heme iron.
Myoglobin is a relatively simple oxygen-binding protein that is found in almost all mammals, primarily in muscle tissue. It facilitates the oxygen diffusion in muscles. Myoglobin is a single polypeptide consisted of 153 amino acid residues with one molecule of heme. It is typical of the family of proteins called globins, all of which have similar primary and tertiary structures.