Allosteric

Allostery refers to a mechanism by which a protein's activity is regulated by the binding of an effector molecule at a site distinct from the active site, called the allosteric site. This binding induces conformational changes that alter the protein's function, often shifting the equilibrium between different structural states. Allosteric regulation is common in enzymes and receptors and can modulate catalytic rate, binding affinity, or signaling output. Effectors are classified as activators or inhibitors and as homotropic (same molecule as substrate) or heterotropic (different molecule).

Most allosteric proteins are oligomeric, and binding of effectors at one site can influence neighboring subunits, producing cooperative behavior. Classic models to describe allostery include the concerted (MWC) model, in which all subunits switch between tense and relaxed states, and the sequential (KNF) model, where ligand binding induces conformational changes in a single subunit that propagate. Allosteric regulation enables rapid and tunable control of metabolic flux and signaling pathways. Examples include the regulation of aspartate transcarbamoylase by CTP and ATP, and the oxygen-carrying protein hemoglobin, whose affinity for oxygen is modulated by effectors such as 2,3-bisphosphoglycerate, protons, CO2, and temperature.

In pharmacology and drug design, allosteric modulators bind to non-active sites to enhance or dampen the effect of orthosteric ligands, offering route to selective modulation with potential advantages such as lower toxicity and saturation of response. Allostery is a general principle across proteins and is central to understanding regulation in biochemistry and cellular signaling.