Serine Proteases

Thomas J. Martin

The serine proteases are a class of proteolytic enzyme (they catalyze the hydrolysis of either ester or peptide bonds in proteins) that require an active site residue for covalent catalysis. The active site residue, the catalytic Ser-195, is particularly activated by hydrogen-bonding interactions with His-57 and Asp-102. Crystal structures show that Ser-195, His-57, and Asp-102 are close in space. Together these three residues, which are located in the substrate binding (S1) pocket, form the famed catalytic triad of the serine proteases. In humans and mammals serine proteases perform many important functions, especially the digestion of dietary protein, in the blood-clotting cascade, and in the complement system:

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Tetrahedral intermediate

Active enzyme

Fig. B.12.1. Schematic diagram of the mechanism of reaction of serine proteases.

Tetrahedral intermediate

Active enzyme

Fig. B.12.1. Schematic diagram of the mechanism of reaction of serine proteases.

• Trypsin, chymotrypsin, and elastase are three of the most important protein-digesting enzymes secreted by the pancreas. Despite their similarities they have different substrate specificity, that is, they cleave different peptide bonds during protein digestion.

• Several activated clotting factors are serine proteases, including thrombin, plasmin, factor 10 (X), and factor 11 (XI).

Several proteins involved in the complement cascade are serine proteases, for example C1r and C1s, and the C3 convertases C4b, 2a and C3b, Bb.

The mechanism of reaction of the serine proteases is depicted schematically in Figure B.12.1; it is divided in an acylation step and a deacylation step.

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