Functional significance of flexibility in proteins.

The structural basis and the functional implications of large—scale flexibility are discussed for three systems: trypsin-trypsinogen, immunoglobulins, and citrate synthase. The trypsin-trypsinogen system provides an example in which an order-disorder transition is used as a means to regulate enzymatic activity. Immunoglobulins demonstrate how flexibly linked domains may be used to allow the binding of ligands with diverse arrangements. In citrate synthase, domain motion forms an active site that is shielded from solvent. Analogous largescale flexibility has been observed in a number of other