Serine protease mechanism and specificity.

Almost one-third of all proteases can be classified as serine proteases, named for the nucleophilic Ser residue at the active site. This mechanistic class was originally distinguished by the presence of the AspHis-Ser “charge relay” system or “catalytic triad”.1 The Asp-His-Ser triad can be found in at least four different structural contexts, indicating that this catalytic machinery has evolved on at least four separate occasions.2 These four clans of serine proteases are typified by chymotrypsin, subtilisin, carboxypeptidase Y, and Clp protease (MEROPS nomenclature;3 Table 1). More recently, serine proteases with novel catalytic triads and dyads have been discovered, including Ser-His-Glu, Ser-Lys/His, His-Ser-His, and N-terminal Ser.2 Several of these novel serine proteases are subjects of accompanying articles in this issue. This article will review recent work on the mechanism and specificity of chymotrypsin-like enzymes, with the occasional references to pertinent experiments with subtilisin. Chymotrypsin-like proteases are the most abundant in nature, with over 240 proteases recognized in the MEROPS database.3 * E-mail: [email protected]; phone: 781-736-2333; FAX: 781-736-2349. 4501 Chem. Rev. 2002, 102, 4501−4523