Section 22.2.7.2. Hydrogen bonds involving sulfur atoms

Sulfur atoms are larger and have a more diffuse electron cloud than oxygen or nitrogen, but are nevertheless capable of participating in hydrogen bonds. Given that the radius of sulfur is ∼0.4 Å greater than that of oxygen, hydrogen bonds can be assumed if the distance H···S is less than ∼2.9 Å, or S···O(N) is less than ∼3.9 Å, providing the angular geometry is right. In proteins, the SH group of cysteine can be a hydrogen-bond acceptor or donor, whereas the sulfur atoms in disulfide bonds and in Met side chains can act only as acceptors.

The clearest example of hydrogen bonding involving Cys residues is given by the NH···S hydrogen bonds in Fe-S proteins (Adman et al., 1975); here, peptide NH groups are oriented to point directly at the S atoms of metal-bound Cys residues, with H···S distances of 2.4–2.9 Å. Similar NH···S hydrogen bonds are found in blue copper proteins, involving the Cys ligands. In these cases, the cysteine sulfur is deprotonated and therefore more negative, making it a stronger hydrogen-bond acceptor, and it is likely that hydrogen bonding to cysteine S⁻ atoms is common. A large survey of Cys and Met side chains in proteins has given evidence of both N—H···S and S—H···O hydrogen bonds involving the SH groups of Cys side chains (Gregoret et al., 1991). In particular, Cys residues in helices frequently hydrogen bond to the main-chain C=O group four residues back in the helix in interactions analogous to those seen for Ser and Thr residues in helices. On the other hand, O—H···S or N—H···S hydrogen bonds to the S atoms of Met or half-cystine side chains, although they do exist, are rare (Gregoret et al., 1991; Ippolito et al., 1990).