| Home |
 |
Chapter 6 |
|
They may take a minute to download, depending on the speed of your link to the Internet. Please be patient.
| Figure 6.23 | Mechanism of chymotrypsin-catalyzed cleavage of a peptide bond. Chymotrypsin is one of a family of enzymes known as the serine proteases and catalyzes the hydrolysis of peptide bonds. Three amino acid residues in the active site of chymotrypsin, His-57, Asp-102 and Ser-195, orchestrate this catalytic activity and are positioned so as to form a hydrogen-bonded network between their side chains. When the substrate enters the active site, it is oriented and held in place by the binding of the side chain, R1, to the binding pocket. Because of the hydrogen-bonded network, the pKa for His-57 is increased and the Ser-195 becomes much more nucleophilic. The Ser-195 attacks the carbonyl of the peptide bond and forms the transition state intermediate (E-TI1). His-57 now acts as an acid catalyst to hydrolyze the peptide bond and the amine product (P1) leaves the active site. Water then enters the active site, donates a proton (H+) to His-57 leaving the OH- to attack the carbonyl of the acyl enzyme. The second transition state (E-TI2) is then stabilized by the hydrogen-bonded network between Ser-195 and His-57 allowing for the hydrolysis and release of the carboxylate product (P2). |
|