Cooperative binding positive cooperativity

Cooperativity, the interaction of molecules on a protein resulting from the mutual binding of those molecules. The cooperativity may be positive (whereby the binding of one of the substances facilitates the interaction of the protein with the other molecule) or negative (binding of one molecule decreases the interaction of the protein with the other molecule). 

The simplest model that can describe allosteric interactions at GPCRs is the ternary complex allosteric model [9], As shown in Figure 1, according to this model two parameters define the actions of allosteric agent (X) its affinity for the unoccupied receptor (Kx) and its cooperativity (a) with the ligand (A) that interacts at the primary binding site a < 1 represents negative cooperativity a = 1, no cooperativity a > 1, positive cooperativity. 

Tucek S, Musilkova J, Neduoma J, Proska J, Shelkovnikov SW, Vorlicek J. Positive cooperativity in the binding of alcuronium and A-methy lscopolamine to muscarinic acetylcholine receptors. Mol Pharmacol 1990 38 674-680. 

Lazareno S, Gharagozloo P, Kuonen D, Popham A, Birdsall NJ. Subtype-selective positive cooperative interactions between brucine analogs and acetylcholine at muscarinic receptors radioligand binding studies. Mol Pharmacol 1998 53 573-589. 

COOPERATIVE ENZYMES do not show a hyperbolic dependence of the velocity on substrate concentration. If the binding of one substrate increases the affinity of an oligomeric enzyme for binding of the next substrate, the enzyme shows positive cooperativity. If the first substrate makes it harder to bind the second substrate, the enzyme is negatively cooperative. 

PHOSPHOFRUCTOKINASE shows positive cooperativity with fructose-e-phosphate as the substrate. ATP, an allosteric inhibitor, binds to the T state and decreases the velocity. AMP, a signal for low energy, binds to the R state and increases the velocity of the reaction. 

The formation of ER dimers can be favored once the first monomer has bound to the DNA, since this presents positive cooperation in binding the next monomer. In any case, DNA binding creates a greater compaction of the dimer that results in a subsequent spatial restructuring of the receptor molecules. 

Boyer, J. L Martinez-Carcamo, M Monroy-Sanchez, J. A., Posadas, C., and Garcia-Sainz, J. A. (1986) Guanine nucleotide-induced positive cooperativity in muscarinic-cholinergic antagonist binding. Biochem. Biophys. Res. Commun. 134,172-177. 

In some earlier publications the term cooperativity is used for positive cooperativity and anticoop-erativity is used for negative cooperativity. In this book cooperativity is used whenever g 1. Sometimes, when there is positive cooperativity one says that a ligand at a supports or favors the binding of a ligand at b, and vice versa. 

---