Covalent catalysis involves formation of a transient covalent intermediate between the enzyme and substrate. Serine proteases (chymotrypsin) use a catalytic triad. The role of the histidine residue in the catalytic triad (Asp-His-Ser) is:

• A Histidine stabilizes the oxyanion hole by donating a hydrogen bond to the carbonyl oxygen of the substrate
• B Histidine directly forms the covalent acyl-enzyme intermediate with the substrate
• C Histidine acts as a general acid-base catalyst: it abstracts the proton from the Ser-OH (increasing nucleophilicity) and donates the proton to the substrate leaving group during acylation ✓
• D Histidine bridges the Asp and Ser residues by covalent disulfide bonds to maintain active site geometry

Explanation

In the chymotrypsin catalytic triad, Asp102 stabilizes the positive charge on His57 by electrostatic interaction, maintaining His57 in a position to accept a proton from Ser195. His57 acts as a general base, abstracting the Ser195 hydroxyl proton (making Ser a potent nucleophile that attacks the peptide carbonyl). After forming the acyl-enzyme intermediate, His57 then donates this proton back to the leaving amino group of the cleaved peptide (acting as general acid). The oxyanion hole is stabilized by backbone NH groups (Gly193 and Ser195 amide protons), not by histidine. Histidine never forms a covalent intermediate itself.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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