---
title: "Serine protease (chymotrypsin) Template | MolDraw"
url: https://www.moldraw.com/templates/enzyme-serine-protease/
description: "Serine protease (chymotrypsin) template: Chymotrypsin cuts a peptide bond in two half-reactions: Ser195 (activated by His57, held by Asp102) attacks the…"
lang: en
publisher: Scidart Academy
generated: 2026-11-13
---
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# Serine protease (chymotrypsin) template

![Serine protease (chymotrypsin) template: Chymotrypsin cuts a peptide bond in two half-reactions: Ser195 (activated by His57, held by Asp102) attacks the carbonyl to give a tetrahedral intermediate in the oxyanion hole, the amine leaves to give the acyl-enzyme, and water hydrolyses the ester the same way.](https://www.moldraw.com/templates/enzyme-serine-protease.webp)

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Chymotrypsin cuts a peptide bond in two half-reactions: Ser195 (activated by His57, held by Asp102) attacks the carbonyl to give a tetrahedral intermediate in the oxyanion hole, the amine leaves to give the acyl-enzyme, and water hydrolyses the ester the same way.

## Mechanism step by step

The catalytic triad Asp102–His57–Ser195: a tetrahedral intermediate, an acyl-enzyme, then hydrolysis by water

1. **Acylation: attack** – His57 takes the Ser195 proton as Ser–O attacks the C=O; Asp102 holds His57–H⁺ in place
2. **Acyl-enzyme** – The O⁻ (in the oxyanion hole) re-forms C=O; the amine N takes H⁺ from His57 and leaves
3. **Deacylation: water attacks** – His57 now activates water; a second tetrahedral intermediate
4. **Release** – C=O re-forms, Ser195 leaves and takes back its proton: free enzyme

## Key points

- Ser195 is made a strong nucleophile by His57 (general base); Asp102 orients His57 and stabilises His57–H⁺ (charge-relay system, Blow et al. 1969).
- The oxyanion of the tetrahedral intermediate is H-bonded by the backbone NHs of Gly193 and Ser195 (the oxyanion hole), which binds the transition state more tightly than the substrate.
- Ping-pong kinetics: the amine leaves before water enters; the covalent acyl-enzyme can be trapped (burst kinetics with p-nitrophenyl acetate).
- The S1 pocket sets specificity: large hydrophobic side chains (Phe, Tyr, Trp) for chymotrypsin, Lys/Arg for trypsin (Asp189), small ones for elastase.

Drawn with 124 atoms, 17 arrows, 8 shapes – every one editable in MolDraw.

## Sources

- [Nelson & Cox, Lehninger Principles of Biochemistry, 8th ed., 2021, ch. 6](https://openlibrary.org/isbn/9781319228002) Textbook
- [Berg, Tymoczko, Gatto & Stryer, Biochemistry, 9th ed., 2019, ch. 9](https://openlibrary.org/isbn/9781319114657) Textbook
- [Blow, Birktoft & Hartley, Nature 1969, 221, 337](https://doi.org/10.1038/221337a0) Original paper

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