Strong hydrophobic nature of cysteine residues in proteins

The differences between disulfide-bonding cystine (CysSS) and free cysteine (CysSH) residues were examined by analyzing the statistical distribution of both types of residue in proteins of known structure. Surprisingly, CysSH residues display stronger hydrophobicity than CysSS residues. A detailed survey of atoms which come into contact with the sulfhydryl group (sulfur atom) of CysSH revealed those atoms are essentially the same in number and variety as those of the methyl group of isoleucine, but are quite different to those of the hydroxyl group of serine. Moreover, the relationships among amino acids were also determined using the 3D-profile table of known protein structures. CysSH was located in the hydrophobic cluster, along with residues such as Met, Trp and Tyr, and was clearly separated from Ser and Thr in the polar cluster. These results imply that free cysteines behave as strongly hydrophobic, and not hydrophilic, residues in proteins.