1. Mechanism of proteolysis by the serine protease chymotrypsin
Mechanism of proteolysis by the serine protease chymotrypsin. In step 1, His 57 acts as general base to extract a proton from Ser 195. Following nucleophilic attack of Ser 195 on the substrate, the His residue shuttles a proton to the now-basic amine of the tetrahedral intermediate (step 2), thus facilitating formation of the acyl-enzyme intermediate (step 3). In step 4, His 57 again serves as general base to accept a proton from the catalytic water molecule as it attacks the acyl-enzyme intermediate. Finally, His 57 shuttles a proton back to Ser 195 as the tetrahedral intermediate breaks down (step 5), releasing the hydrolyzed product and regenerating the enzyme (step 6). (Reproduced, with permission, from Murray RK, Bender D, Botham KM, Kennelly PJ, Rodwell VW, Weil PA. Harper’s Illustrated Biochemistry. 29th ed. New York: McGraw-Hill Education; 2012.)
Source: Reactions of Carbonyl Species, The Organic Chemistry of Medicinal Agents
Citation: Renslo A. The Organic Chemistry of Medicinal Agents; 2016 Available at: Accessed: October 29, 2017
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