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The Hill coefficient, or , may describe cooperativity (or possibly other biochemical properties, depending on the context in which the Hill equation is being used). When appropriate, [clarification needed] the value of the Hill coefficient describes the cooperativity of ligand binding in the following way:
The first description of cooperative binding to a multi-site protein was developed by A.V. Hill. [4] Drawing on observations of oxygen binding to hemoglobin and the idea that cooperativity arose from the aggregation of hemoglobin molecules, each one binding one oxygen molecule, Hill suggested a phenomenological equation that has since been named after him:
One manifestation of this is enzymes or receptors that have multiple binding sites where the affinity of the binding sites for a ligand is apparently increased, positive cooperativity, or decreased, negative cooperativity, upon the binding of a ligand to a binding site. For example, when an oxygen atom binds to one of hemoglobin's four binding ...
This model explains sigmoidal binding properties (i.e. positive cooperativity) as change in concentration of ligand over a small range will lead to a large increase in the proportion of molecules in the R state, and thus will lead to a high association of the ligand to the protein. It cannot explain negative cooperativity.
Negative cooperativity occurs when binding of the first substrate decreases the affinity of the enzyme for other substrate molecules. Allosteric enzymes include mammalian tyrosyl tRNA-synthetase, which shows negative cooperativity, [37] and bacterial aspartate transcarbamoylase [38] and phosphofructokinase, [39] which show positive cooperativity.
The sequential model (also known as the KNF model) is a theory that describes cooperativity of protein subunits. [1] It postulates that a protein's conformation changes with each binding of a ligand, thus sequentially changing its affinity for the ligand at neighboring binding sites.
Hofmeyr and Cornish-Bowden first published the reversible form of the Hill equation. [1] The equation has since been discussed elsewhere [ 3 ] [ 4 ] and the model has also been used in a number of kinetic models such as a model of Phosphofructokinase and Glycolytic Oscillations in the Pancreatic β-cells [ 5 ] or a model of a glucose-xylose co ...
where is the Hill coefficient which quantifies the steepness of the sigmoidal stimulus-response curve and it is therefore a sensitivity parameter. It is often used to assess the cooperativity of a system. A Hill coefficient greater than one is indicative of positive cooperativity and thus, the system exhibits ultrasensitivity. [34]