Valine 108, a chain-folding initiation site-belonging residue, crucial forthe ribonuclease a stability

Thermal denaturation of bovine pancreatic ribonuclease A and a set of its s ingle variants, carrying replacements of hydrophobic residues in the postul ated 106-118 chain folding initiation site, has been studied by differentia l scanning calorimetry. Ribonuclease A variants undergo a two-state thermal transition denaturation except for those with replacement of valine 108. M ost mutations cause a significant destabilization of the protein compared t o the wild-type, thus demonstrating the importance of hydrophobic residues at the 106-118 region in maintaining the stability of the molecule. Among t hem, those of valine 108 promote the greatest (14-27 degrees C) destabiliza tion of the molecule. Therefore, valine 108 plays a crucial role for ribonu clease A stability. (C) 1999 Academic Press.