Ligand-induced conformational changes in proteins

Abstract

The natures and roles of ligand-induced conformational changes are described in terms of the influence of the ligand on the equilibrium distribution of the protein structure among various conformational states. A very commonly observed conformational change is produced by a ligand binding into a cleft that lies between two domains and then closing the cleft through a hinge-like motion. Such a change in hexokinase serves to bring potential catalytic groups into the active site and to provide a binding site for the three phosphates of ATP. Flexibility in gene regulatory proteins such as the Escherichia coli catabolite activator protein and lac repressor may be important in the dual requirement for rapid diffusion of the proteins along the DNA as well as specific recognition of base sequences. A second role for flexibility in this class of proteins is to reduce their affinity for affinity for DNA, without reducing their capacity to discriminate among sequences.