Disulfide bonds have been shown to stabilize proteins (i.e., make them less likely to unfold). Consider the

Question:

Disulfide bonds have been shown to stabilize proteins (i.e., make them less likely to unfold). Consider the cases shown schematically below for two variants of the same protein. In case #1 the disulfide forms between Cys residues that have been introduced near the protein N- and C-termini, and in case #2 the disulfide forms between Cys residues that have been introduced in the middle of the protein sequence. Which protein is likely to be more stable? (Note: Assume the disulfide bond is intact in both the unfolded and folded states). Explain your reasoning.

N s-s- D Case #1: Disulfide forms near termini N S-S- Case #1: Disulfide forms in middle of protein