On the fundamental role of the glu 2 −…Arg 10 + salt bridge in the folding of isolated ribonuclease a S-peptide

The fundamental role of the Glu 2 −…Arg 10 + salt bridge in the folding of isolated S-peptide (1–19 N-terminal fragment of Ribonuclease A) is demonstrated from the comparison of the helix contents, at 0°C, of S-peptide and related peptides. Helix contents have been determined from the analysis of proton chemical shift vs. temperature curves. The observed data can be accounted for by assuming that two side-chain interactions contribute to stabilize the 3–13 helix of S-peptide, the salt bridges Glu 2 −…Arg 10 + and Glu 9 −…His 12 +, the former being more effective. The salt bridge Glu 2 −…Arg 10 + turns to a weaker interaction, a hydrogen bond Glu 2 (C δ=0)…Arg 10 +, on protonation or esterification of the Glu 2 carboxylate.