allosterically

Allosterically refers to processes governed by allostery, the regulation of a protein's activity through binding at a site other than the active site, called an allosteric site. Binding at this site induces conformational changes that alter the protein’s function, often changing substrate affinity or catalytic rate. Allostery is a key mechanism of metabolic control and signaling and can affect enzymes, receptors, and other multimeric proteins.

Mechanistically, allosteric regulation typically involves shifts in the conformational ensemble of a protein. In enzymes, these shifts can modulate the active site geometry or accessibility. Classic models describe cooperative transitions between low-activity (T) and high-activity (R) states, as in the Monod-Wyman-Changeux and Koshland-Némethy-Filmer frameworks. Effectors acting at allosteric sites can be activators or inhibitors, and may be homotropic (the effector is the substrate) or heterotropic (a different molecule acts as the effector). The result is often a non-Michaelis–Menten kinetic profile that reflects allosteric modulation.

Examples commonly cited include hemoglobin, where oxygen binding and allosteric effectors like 2,3-bisphosphoglycerate influence oxygen affinity, and metabolic enzymes such as aspartate transcarbamoylase (ATCase) regulated by ATP and CTP, or phosphofructokinase, controlled by ATP, AMP, and citrate. Allosteric regulation is widespread across biology and is a focus of pharmacology, where allosteric modulators can fine-tune protein activity. Positive allosteric modulators enhance function, while negative allosteric modulators reduce activity, often producing effects that are saturable and context-dependent. Allosterically describes actions that rely on these distal binding events and conformational communications within multimeric proteins.