Allostery

Allostery is the regulation of a protein’s activity through the binding of an effector at one site, the allosteric site, that induces a functional change at a distant site, often the active site. It frequently involves conformational changes between distinct states with different activities. In oligomeric proteins, communication between subunits allows binding of ligand to one subunit to alter the affinity or activity of other subunits.

Two classic models describe allosteric regulation. The Monod-Wyman-Changeux (MWC) concerted model posits that the protein exists in equilibrium between tense (inactive) and relaxed (active) states, with all subunits switching together. The Koshland-Némethy-Filmer (KNF) sequential model allows subunits to change state one at a time upon ligand binding. In practice, many systems display features of both models. Ligands can be homotropic (the substrate itself acts as the effector) or heterotropic (a different molecule acts as the effector). An iconic example is hemoglobin, where oxygen binding increases the affinity of remaining sites, displaying cooperative allostery. Enzymes such as aspartate transcarbamoylase and phosphofructokinase also show allosteric regulation by small molecules that activate or inhibit activity.

Allosteric sites provide targets for drug design, offering specificity and tunable responses. Studying allostery integrates structural, kinetic, and thermodynamic data to understand changes in conformation, dynamics, and energy landscapes that underlie regulatory effects.