Covalent catalysis is the mechanism used by serine protease enzymes. In the catalytic mechanism of chymotrypsin, which three amino acid residues form the catalytic triad and what are their functions?
- A Ser-195 (nucleophile), His-57 (general base/acid), Asp-102 (orients and stabilises His via hydrogen bond) — the charge relay system ✓
- B Ser-195 (electrophile), Lys-57 (proton donor), Asp-102 (general acid) — the charge relay system
- C Thr-195 (nucleophile), His-57 (acid-base), Glu-102 (electrostatic stabilisation)
- D Ser-195 (nucleophile), His-57 (general base), Cys-102 (forms a disulfide with Ser to stabilise the catalytic cleft)
Correct answer: A. Ser-195 (nucleophile), His-57 (general base/acid), Asp-102 (orients and stabilises His via hydrogen bond) — the charge relay system
Explanation
Serine proteases (chymotrypsin, trypsin, elastase, thrombin, factor Xa) share the canonical catalytic triad: Ser-195 acts as the nucleophile attacking the carbonyl carbon of the peptide bond; His-57 acts as a general base (accepting the proton from Ser-195) and then as a general acid (donating the proton to the leaving amine); Asp-102 is hydrogen-bonded to His-57, stabilising the positive charge on His (imidazolium) during the tetrahedral intermediate. This constitutes the charge relay system. The catalytic mechanism proceeds via a covalent acyl-enzyme intermediate.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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