Different Types of Interactions Involving Cysteine Sulfhydryl Group in Proteins

Abstract

Various types of interactions involving the sulfhydryl group of free cysteine residues have been analyzed using known protein structures. In a hydrogen bond the -SH group is more amenable to donating its proton to a carbonyl group, rather than acting as a proton acceptor. It rarely interacts with a carboxylate group, and is a poor ligand to bind an anionic substrate. It is quite prone to make contacts that are definitely non-hydrogen bond type. In the S…C=0 interaction the S atom is placed on the face of an amide group (mostly from the main-chain, but there are cases from the side-chain also) close to the C atom. Cases of S…N interaction, where the S atom is on top of the N atom of another residue (both main-, as well as side-chains, including the guanidinium group) are also observed. A considerable number of Cys residues have aromatic residues as neighbors, and here too, the preferred mode of interaction is along the face. The intra-residue S…C=0 interaction constrains the main-chain and side-chain torsion angles (ψ and x1), whereas the inter-residue interactions are non-local and stabilize the tertiary structure. The S…C=0 interaction may have a role in lowering the pK avalues of the Cys residues in enzyme active sites.