Ligand Binding and Linkage

Most proteins have multiple locations where ligands can associate, in addition to the site responsible for protein function. Binding of a molecule to any of these sites often results in conformational changes, altering the shape of the protein.

When this change affects the binding of another ligand,  the two sites are described as coupled or linked. The binding site linkage can be positively or negatively regulated.

In a positive linkage, the binding of one ligand results in conformational changes that make another site more likely to bind to its respective ligand. 

In a negative linkage, the binding of one ligand results in conformational changes that prevent another binding site from associating with its ligand.