69. Which of the following amino acid changes in the active site of an enzyme is most likely to change its
activity?
1. Lys → Arg
2. Leu → Ile
3. Glu → Asp
4. Lys → Pro
Introduction
Enzymes are biological catalysts that accelerate chemical reactions by lowering the activation energy. The specific shape and chemistry of the enzyme’s active site play a crucial role in its ability to bind substrates and catalyze reactions. Even small changes in the amino acid sequence of the active site can significantly impact the enzyme’s function. Let’s take a look at which amino acid substitutions are most likely to affect enzyme activity.
Understanding the Active Site
The active site of an enzyme is the region where substrate molecules bind and undergo chemical reactions. The structure and chemical properties of amino acids in this site are crucial for the enzyme’s function. For example:
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Electrostatic interactions: Amino acids like lysine (positively charged) or glutamic acid (negatively charged) participate in ionic interactions with substrates.
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Hydrophobic interactions: Non-polar amino acids like leucine or isoleucine help maintain the enzyme’s structural integrity.
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Hydrogen bonding: Polar amino acids such as glutamine or serine can form hydrogen bonds with substrates or co-factors.
Evaluating the Amino Acid Changes
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Lys → Arg:
Both lysine (Lys) and arginine (Arg) are positively charged amino acids, and they are similar in size and structure. However, arginine has a larger side chain with an additional guanidino group. This change may not drastically alter enzyme activity, but it could have a subtle effect on enzyme function, particularly in enzyme-substrate interactions where charge or steric properties are important. -
Leu → Ile:
Leucine (Leu) and isoleucine (Ile) are both hydrophobic amino acids with very similar structures. Their side chains only differ by the position of the methyl group. Therefore, this substitution is less likely to have a large effect on enzyme activity, especially if the enzyme’s active site relies on hydrophobic interactions. -
Glu → Asp:
Glutamic acid (Glu) and aspartic acid (Asp) are both negatively charged amino acids, but glutamic acid has an extra methylene group in its side chain compared to aspartic acid. This substitution might cause only minor structural changes, but it could still affect the enzyme’s ability to interact with other charged molecules or substrates in its active site. -
Lys → Pro:
Lysine (Lys) is a positively charged amino acid, while proline (Pro) is a unique amino acid with a cyclic side chain that causes a rigid kink in the polypeptide chain. Substituting lysine with proline is likely to cause a significant disruption in the enzyme’s active site. This change can interfere with the enzyme’s overall structure, flexibility, and the ability to form appropriate interactions with its substrates or co-factors.
Conclusion
Among the listed options, the Lys → Pro substitution is most likely to have the most profound effect on enzyme activity. Proline’s unique structure can disrupt the enzyme’s conformation and hinder its ability to properly bind substrates, making it the most likely amino acid change to alter enzyme activity significantly.
Therefore, the correct answer is:
4. Lys → Pro
