Think about the type of reaction that is catalyzed by chymotrypsin. Which single mutation would be most likely to make deltaGo' for this reaction more positive? O None of mutation options is suitable because none of these mutations is expected to change deltaGo' at all.

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### Understanding the Effect of Mutations on the Catalytic Activity of Chymotrypsin

#### Problem Statement

Consider the enzymatic reaction catalyzed by chymotrypsin. Reflect on how single amino acid mutations could influence the reaction’s standard free energy change (\( \Delta G^\circ \)).

**Question:**
Which single mutation would be most likely to make \( \Delta G^\circ \) for this reaction more positive?

**Options:**
- \( \bigcirc \) None of the mutation options is suitable **because** none of these mutations is expected to change \( \Delta G^\circ \) at all.
- \( \bigcirc \) None of the mutation options is suitable **because** these mutations are more likely to make \( \Delta G^\circ \) more negative.
- \( \bigcirc \) Asp → Ala
- \( \bigcirc \) His → Ala
- \( \bigcirc \) Ser → Ala

Notice that the enzyme chymotrypsin has specific residues critical for its catalytic function, and altering these residues can change the reaction's standard free energy.

### Explanation

Chymotrypsin is a serine protease enzyme that catalyzes the hydrolysis of peptide bonds. It has a catalytic triad consisting of aspartic acid (Asp), histidine (His), and serine (Ser), which are key to its enzymatic action. Mutating any of these residues can impact the enzyme's catalytic efficiency and consequently affect the reaction’s \( \Delta G^\circ \).

**Mutation Effects:**
- **Asp → Ala**: Replacing aspartic acid with alanine could disrupt the enzyme's active site, potentially making \( \Delta G^\circ \) more positive (less favorable) because Asp is crucial for stabilizing the transition state.
- **His → Ala**: Histidine plays a critical role in proton transfer within the catalytic triad. Replacing it with alanine can significantly affect the enzyme's functionality, making \( \Delta G^\circ \) more positive.
- **Ser → Ala**: Serine is directly involved in the nucleophilic attack on the peptide bond. Mutating it to alanine can severely impact catalytic activity, likely increasing \( \Delta G^\circ \).

In this scenario, each mutation provided (Asp → Ala, His → Ala, Ser → Ala) is expected to disrupt the catalytic function of chymotrypsin
Transcribed Image Text:### Understanding the Effect of Mutations on the Catalytic Activity of Chymotrypsin #### Problem Statement Consider the enzymatic reaction catalyzed by chymotrypsin. Reflect on how single amino acid mutations could influence the reaction’s standard free energy change (\( \Delta G^\circ \)). **Question:** Which single mutation would be most likely to make \( \Delta G^\circ \) for this reaction more positive? **Options:** - \( \bigcirc \) None of the mutation options is suitable **because** none of these mutations is expected to change \( \Delta G^\circ \) at all. - \( \bigcirc \) None of the mutation options is suitable **because** these mutations are more likely to make \( \Delta G^\circ \) more negative. - \( \bigcirc \) Asp → Ala - \( \bigcirc \) His → Ala - \( \bigcirc \) Ser → Ala Notice that the enzyme chymotrypsin has specific residues critical for its catalytic function, and altering these residues can change the reaction's standard free energy. ### Explanation Chymotrypsin is a serine protease enzyme that catalyzes the hydrolysis of peptide bonds. It has a catalytic triad consisting of aspartic acid (Asp), histidine (His), and serine (Ser), which are key to its enzymatic action. Mutating any of these residues can impact the enzyme's catalytic efficiency and consequently affect the reaction’s \( \Delta G^\circ \). **Mutation Effects:** - **Asp → Ala**: Replacing aspartic acid with alanine could disrupt the enzyme's active site, potentially making \( \Delta G^\circ \) more positive (less favorable) because Asp is crucial for stabilizing the transition state. - **His → Ala**: Histidine plays a critical role in proton transfer within the catalytic triad. Replacing it with alanine can significantly affect the enzyme's functionality, making \( \Delta G^\circ \) more positive. - **Ser → Ala**: Serine is directly involved in the nucleophilic attack on the peptide bond. Mutating it to alanine can severely impact catalytic activity, likely increasing \( \Delta G^\circ \). In this scenario, each mutation provided (Asp → Ala, His → Ala, Ser → Ala) is expected to disrupt the catalytic function of chymotrypsin
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