Serine proteases such as trypsin, chymotrypsin, and elastase share a catalytic triad (Ser-His-Asp). The serine acts as a nucleophile, attacking the peptide carbonyl carbon. Which catalytic mechanism is used by covalent acyl-enzyme intermediate formation?

• A Metal-ion catalysis where the Asp residue coordinates a zinc ion to activate serine
• B Covalent catalysis only, with Ser directly attacking the substrate without histidine assistance
• C Acid-base catalysis where His acts as a base, abstracting a proton from Ser, increasing its nucleophilicity ✓
• D Proximity and orientation effects only, positioning substrate for spontaneous hydrolysis

Explanation

In the serine protease catalytic mechanism, the catalytic triad operates through acid-base catalysis. The carboxylate of Asp-102 hydrogen-bonds to His-57, increasing the basicity of histidine. His-57 then acts as a general base by abstracting the proton from Ser-195 hydroxyl, dramatically increasing the nucleophilicity of the serine oxygen. The activated serine oxygen attacks the peptide carbonyl carbon, forming a tetrahedral oxyanion intermediate stabilized by the 'oxyanion hole' (backbone NH groups of Gly-193 and Ser-195). This leads to formation of the covalent acyl-enzyme intermediate and release of the first product (amine). Water then acts as nucleophile, aided by His-57 as acid-base, to hydrolyze the acyl-enzyme and release the second product (carboxylate). This is the paradigmatic mechanism for covalent catalysis with acid-base assistance.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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