Quick Review of Allosteric Enzymes.
A. Regulatory proteins composed of multiple subunits that carry
1. Catalytic sites specific for substrate
2. Regulatory sites for binding of effectors that modulate the enzyme activity (Monod, Changeux & Jacob, 1963; Perutz, 1990).
B. Essential features:
1. COOPERATIVITY: Subunits forming the protein interact in such a manner that the binding of an effector or substrate to one of the sites facilitates (positive cooperativity) or impedes (negative cooperativity) the binding of ligands to the remaining free sites.
2. SIGMOID velocity curve. Several models have been proposed.
a. Phenomenological model for the binding of oxygen to haemoglobin (Hill, 1910).
1. Supposes simultaneous binding of "n" molecules of ligand to the protein.
b. Models based on molecular mechanisms (Adair, 1925; Monod et al., 1965; Koshland, Nemethy & Filmer, 1966).
1. In the latter two models, each subunit of the enzyme exist in two conformational states, which may differ in their affinity for the ligand.
2. In Monod (et al., 1965) mode, the transition of all subunits between these states is "concerted," i.e., correlated.
3. In KNF (1966) model - the transition is sequential: hybrid states formed by different numbers of subunits the two states.
c. Covalent modification another example of enzyme regulation leading to sigmoid kinetics.
1. Exemplified by phosphorylation - dephosphorylation (Krebs & Beavo, 1979; Goldbeter & Koshland, 1981; 1982; 1984; 1987; Koshland, Goldbeter & Stock, 1982; Martiel & Goldbeter, 1981).
3. Enhanced sensitivity to variations in concentration of an effector or substrate.