Allosteric regulation

In the fields of biochemistry and pharmacology an allosteric regulator (or allosteric modulator) is a substance that binds to a site on an enzyme or receptor distinct from the active site, resulting in a conformational change that alters the protein's activity, either enhancing or inhibiting its function. In contrast, substances that bind directly to an enzyme's active site or the binding site of the endogenous ligand of a receptor are called orthosteric regulators or modulators.

The site to which the effector binds is termed the allosteric site or regulatory site. Allosteric sites allow effectors to bind to the protein, often resulting in a conformational change and/or a change in protein dynamics.^[1][2] Effectors that enhance the protein's activity are referred to as allosteric activators, whereas those that decrease the protein's activity are called allosteric inhibitors.

Allosteric regulations are a natural example of control loops, such as feedback from downstream products or feedforward from upstream substrates. Long-range allostery is especially important in cell signaling.^[3] Allosteric regulation is also particularly important in the cell's ability to adjust enzyme activity.

The term allostery comes from the Ancient Greek allos (ἄλλος), "other", and stereos (στερεός), "solid (object)". This is in reference to the fact that the regulatory site of an allosteric protein is physically distinct from its active site. Allostery contrasts with substrate presentation which requires no conformational change for an enzyme's activation. The term orthostery comes from the Ancient Greek orthós (ὀρθός) meaning “straight”, “upright”, “right” or “correct”.