You are studying the effects of amino acid replacements on the stability of a pa

Question

You are studying the effects of amino acid replacements on the stability of a particular alpha helix that is buried in the protein myoglobin. You carry out a series of replacements of a particular leucine residue located in the helix, using site- directed mutagenesis. The replacements are as follows: Leu to Arg Leu to Val Leu to Pro Leu to Ser A. For each replacement, predict whether the change would stabilize, destabilize or have no effect on the structure of the alpha helix. Briefly explain each of your predictions. B. If the codon of the Leucine residue is Cuu. (or CTT in the DNA coding sequence) determine the DNA base positions in the coding strand that would need to be mutated to encode for each of the four amino acid changes listed above. Recall that the most straightforward and least time consuming experiment will be to change as few bases as possible. Paragraph B l : i- Leu to Arg There would be no effect because they have the same 21 Kcalmol helical propensity cuu to CGG Leu to Val It would stabilize because Val has a propensity of 61 Kcal/mol. cUU to GUC Leu to Pro: It would destabilize because Pro is 3.16 Kcal/mol.

Explanation / Answer

There are some changes in your answer

A. In first case, substitution of leucine with arginine destabilize the structure because leucine is a non polar amino acid whereas arginine is a polar amino acid.

In this example, there will no effect because both leucine and Valine are hydrophobic amino acid and non polar amino acid.

In this example, leucine to proline substitution, increase the stability because praline have big aliphatic side chains and more hydrophobic than leucine

In this example substitution of leucine with serine destabilize the alpha helical structure because serine is polar and hydrophilic whereas leucine is non polar and hydrophobic.

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