Basics of Biochemistry Allosteric Enzyme Ashish Kr Dwivedi, PhD
+ Activator No effector + Inhibitor 0 Effect of activators and inhibitors on the sigmoidal kinetics of an enzyme subject to Substrate concentration allosteric control.
AII O All
Two general models for the interconversion of inactive and active forms of a protein during cooperative ligand binding. Although the models may be applied to any protein-including any enzyme that exhibits cooperative binding, we show here four subunits because the model was originally proposed for hemoglobin. (a) In the concerted, or all-or- none, model (MWC model), all subunits are postulated to be in the same conformation, either all circles (low affinity or inactive) or all squares (higlh affinity or active). Depending on the equilibrium, Ki, between circles and squares forms, the binding of one or more ligand molecules (L) will pull the equilibrium toward the square form. Subunits with bound L are shaded. (b) In the sequential model, each individual subunit can be in either the or form. A very large number of conformations is thus possible.
[PL [Pl Ka kd binding sites occupied [PL PILI kd [PL] ka total binding sites [PLI [P Ad IL] KalLI][P] [P] KaL1 Kd Ka [LJ L] Kd log ) n log [L]-log Ka 1- 0
Hill equation, and a plot of log / )1 versus log [L] is called a Hill plot. Based on the equation, the Hill plot should have a slope of n. However, the experimentally determined slope actually reflects not the number of binding sites but the degree of interaction between them. The slope of a Hill plot is therefore denoted by nH, the Hill coefficient, which is a measure of the degree of cooperativity. If nH equals 1, ligand binding is not cooperative, a situation that can arise even in a multisubunit protein if the subunits do not communicate. An nH of greater than 1 indicates positive cooperativity in ligand binding. This is the situation observed in hemoglobin, in which the binding of one molecule of ligand facilitates the binding of others.
Ashish Kr Dwivedi
Former Scientist (IIT Kanpur), Authored 10+ Peer Reviewed International Publications, PhD (IITK) Chief Mentor Triyambak Life Sciences