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Leucine is replaced in a protein with Ala or with Asn which substituion would you expect...

Leucine is replaced in a protein with Ala or with Asn which substituion would you expect to disrupt protein structure the most?

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Answer #1

Mutations on surface residues are less likely to disrupt the fold of a protein but more likely to interfere with the protein interactions (e.g. the solvent). Depending on where your site is located and the role of the residue, an exchange of something very bulky (e.g. M, F, W, Y) to Ala MAY cause dramatic changes in local structure.

But further loss in activity was observed in a peptide in which two of the leucine residues were replaced with alanine (ALDKAEESNSKADKVNVKLT), and a peptide which had all leucine residues in the zipper motif replaced with alanine (ALDKAEESNSKADKVNVKLT) had no inhibitory activity(ref.https://www.ncbi.nlm.nih.gov/pubmed/9527912)

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