Serine Protease (thing)
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A protease is an enzyme that cleaves peptide bonds. A Serine protease is an enzyme that uses an active site serine, in catalysis. They cleave on the C-terminals of specific residues. Trypsin cleaves on the C-terminal of the positively charged amino acids Lysine and Arginine. Chymotrypsin cleaves on the C-terminals of the large aromatic amino acids Phenylalanine, Tyrosine, and Tryptophan. Other Serine proteases include; elastase, thrombin, plasmin and kallikrien.Key Components of the Enzyme Are:
The sketch is a little off scale but should give a fairly good idea of what the arrangement of the active site is.
Key: ... = Hydrogen bond Gly193 | |-----| N | | oxyanion | | | specificty pocket hole H ____| |_____ Ser195 N-H Ser195-CH2-O | | H . . ---N His57 || \\ \ || / \-------N | H . . - O | C==O | | / / Asp102The Mechanism of the Enzyme:
1) In the first step His57 acts as a general base partially abstracting the hydroxyl proton of Ser195. This causes the hydroxyl group on Ser195 to nucleophilically attack the Carbonyl carbon of the scissile bond forming the tetrahedral intermediate. In this intermediate the negative charge on the carbonyl oxygen is stabilized by the oxyanion hole, and His57 is protonated.
2) In the second step the amino end of the scissile bond acts as a leaving group, this is the actual cleavage of the peptide bond. His57 acts as a general acid by protonating this leaving group. At the end of this step His57 is unprotonated, a free peptide fragment has been released, and the hydroxy O of Ser195 is covalently bound to the Carbonyl carbon of the scissile bond.
3) In the third step His57 once again acts as a general base by abstracting a proton from a water molecule, this causes the oxygen of the water molecule to nucleophilically attack the carbonyl carbon. The negative charge on the carbonyl oxygen is once again stabilized by the oxyanion hole. At the end of this step His57 is once again protonated, and another tetrahedral intermediate is formed.
4) In the fourth and final step the hydroxyl oxygen of Ser195 acts as a leaving group, and is protonated by His57 acting as a general acid. This releases a second peptide fragment and regenerates the active site as seen in the diagram.