The active site is a cylindrical tunnel, with the cleavage machinery at its center. Somehow, a polypeptide must be threaded through this tunnel in order for the cleavage reaction to occur. This problem is solved through the use of two flexible flaps that cover the top of the tunnel. When free in solution, these flaps are disordered, opening a path to the active site. When the protease wraps around its target, the flaps close, forming a stable structure that positions the polypeptide accurately for cleavage.
Flexible linkages are common in the molecular world.
Protein chains may be made more flexible through addition of many molecules of the amino acid glycine, which are less hindered in bond rotation because of the lack of a side chain, or through addition of many charged residues, which favor exposure to solvent over forming a compact globule. The rigid kink formed by proline, surprisingly, is also commonly found in flexible regions, because it does not fit comfortably within compactly folded structures. The immune system contains many examples of flexible linkages that enhance multivalent binding, as shown in Figure 9. The entire discipline of biotechnology has emerged to harvest this rich field of biological wealth. We routinely edit and rewrite the information in DNA to build custom proteins tailored for a given need.