Allosterik

Allosterik (often written allosteric in English) refers to the regulation of a protein’s activity through the binding of an effector molecule at a site other than the active site. This allosteric site binding induces conformational changes that modulate the protein’s function, either enhancing or inhibiting activity. Allosteric regulation is widespread in enzymes, receptors, and signaling proteins, and can influence processes from metabolism to gene expression.

In enzymes, allostery frequently produces cooperative substrate binding, leading to sigmoidal rather than Michaelis–Menten kinetics. Two classical conceptual models describe how allostery works: the concerted model (Monod-Wyman-Changeux) posits that proteins switch between distinct T (tense) and R (relaxed) states as a whole, while the sequential model (Koshland-Nemethy-Filmer) suggests gradual, intermediary state changes upon ligand binding. Either way, binding at a non-active site alters the equilibrium between functional states.

Prominent examples include hemoglobin, where oxygen binding at one site increases affinity at remaining sites, and aspartate transcarbamoylase (ATCase), regulated by ATP and CTP through feedback and feedforward mechanisms. Allosteric regulation also occurs in regulatory subunits of multi-subunit enzymes, signaling receptors, ion channels, and many transcription factors. Allosteric effectors can be positive (activators) or negative (inhibitors), providing a means for integration of cellular signals and metabolic control.

Clinically and biotechnologically, allosteric modulators are valuable because they can offer greater selectivity and subtler control than active-site inhibitors. Researchers study allostery through structural biology, spectroscopy, and kinetic analyses to understand conformational dynamics and design therapeutic agents.