Allosteric Regulation

Allosteric regulation is the control of a protein's activity by a molecule that binds at a site other than its active site. The binding changes the shape of the protein, turning its activity up or down, and it allows enzymes to respond to the needs of the cell.

An allosteric protein can switch between a more active and a less active shape. An activator stabilizes the active shape and an inhibitor stabilizes the inactive one. The term comes from Greek words for "other shape" and was introduced by Jacques Monod and François Jacob in 1961. The Monod-Wyman-Changeux model of 1965 and the Koshland-Némethy-Filmer model of 1966 describe how the subunits of a protein change shape together.

Hemoglobin binds oxygen cooperatively, so that binding at one subunit makes it easier at the next, which gives it an S-shaped binding curve. Phosphofructokinase, a key enzyme of glycolysis, is inhibited by high levels of ATP and stimulated by AMP, linking the pathway to the cell's energy state. In feedback inhibition, the final product of a pathway, such as CTP in pyrimidine synthesis, blocks the first enzyme of that pathway.

Drugs that bind allosteric sites can be more selective than those that bind the active site, because allosteric sites vary more between related proteins. Many receptors on cell surfaces are modulated this way. Computational tools, including AI structure prediction, are used to find such sites, and the regulation of ATP synthesis and metabolism depends on them throughout.

• Enzymes — the proteins most often regulated this way
• Active Site — the site it acts on indirectly
• Glycolysis — a pathway with allosteric control points