Proteases--structures, mechanism and inhibitors.

Proteases have been divided into four mechanistic classes: serine proteases, metalloproteases, aspartic proteases, and cysteine proteases. Once a new enzyme is classified by the use of general inhibitors, it is possible to design reactive inhibitors by using mechanistic information learned through study of other members of the same protease family. The most useful types of inhibitors for serine proteases are transition-state inhibitors including alpha-ketoesters and phosphonates, and mechanism-based inhibitors such as heterocyclic isocoumarin inhibitors. Some of these inhibitors are quite specific toward individual target serine proteases. Many proteases are involved in various disease states, and potent inhibitors of these enzymes have the potential to be developed as new therapeutic agents. In the future, it is likely than numberous specific protease inhibitors will be tested clinically for the treatment of human disease.