Allosteri

Allosteri refers to allostery, the regulation of protein activity through binding at an allosteric site, distant from the active site. Binding induces conformational changes that alter activity, often modulating affinity for substrates or catalytic rate.

Mechanisms: Allosteric sites bind effectors which can be activators or inhibitors. Two classic models: the concerted (MWC) model posits that subunits change conformation together, while the sequential (KNF) model allows successive conformational changes in subunits. The structural transition propagates signals across the protein, changing its function.

Examples: Hemoglobin exhibits allostery; enzymes such as aspartate transcarbamoylase (ATCase) and phosphofructokinase-1 are regulated allosterically. Allosteric regulation is common in metabolic pathways and signaling receptors. Allosteric drugs target allosteric sites to modulate function with often greater selectivity and fewer side effects than active-site inhibitors.

Applications and research: Understanding allostery is central to biochemistry and pharmacology. Techniques include X-ray crystallography, cryo-electron microscopy, NMR, and kinetic studies; computational models also contribute. Engineering allosteric control is used in synthetic biology and enzyme design.

Etymology and history: The term derives from Greek allos meaning "other" and stereos meaning "shape" or "form." The concept was introduced in the 1960s by Monod, Wyman, and Changeux, and has since become a foundational principle in the regulation of protein activity.