Sandbox 50: Difference between revisions

Trypsin's active site is composed of its catalytic triad, three amino acid residues that are crucial to the enzymes proteolytic function. The catalytic triad consists of Asp 102, His 57, and Ser 195. Serine is the major player in the cleaveage of the peptide bond, thus the name serine protease. His 57 and Asp 102 aid in the cleavage by hydrogen bonding and electrostatically stabalizing the substrate. Ser 195 performs a nucleophilic attack on the substrate's peptide carbonyl. This causes the oxyanion hole to form. The nucleophilic attack by the oxygen of Ser 195 also forms a tetrahedral intermediate. By reconstruction of the carbonyl double bound, the amino portion of the peptide leaves as a product, and an acyl-enzyme intermediate is left in the active site. Now the active site needs to be regenerated. To do this a water molecule nucleophillically attacks the carbonyl carbon, forming another tetrahedral intermediate and reforming the oxyanion hole. The nitrogen of the His 57 ring makes the oxygen of the water more nucleophilic by hydrogen bonding to one of water's oxygens. By reforming the double bond of the carbonyl carbon, the carboxy end of the original substrate's peptide bond is released, and the active site has been regenerated. The picture in the thumbnail to the left shows the entire catalytic mechanism for a serine protease. A figure of the oxyanion whole can be seen in greater detail in the thumbnail on the left.