disulfidebond

A disulfide bond, also called a disulfide bridge, is a covalent linkage between two sulfur atoms, typically the thiol groups of cysteine residues in proteins, forming an -S–S- linkage. It arises by oxidation of two thiol groups and can be reduced back to free thiols. In biological systems, disulfide bonds form mainly in oxidizing environments such as the endoplasmic reticulum and extracellular space, where enzymes like protein disulfide isomerase (PDI) and related oxidoreductases catalyze their formation, reshuffling, and isomerization.

Disulfide bonds can be intramolecular, connecting two parts of the same polypeptide to stabilize tertiary structure, or intermolecular, linking different polypeptides to stabilize quaternary assemblies. They play a key role in protein folding, stability, and resistance to proteolysis. Some disulfide bonds are redox-regulated, altering a protein’s activity in response to cellular conditions.

Examples include the disulfide patterns in insulin, which contains two interchain and one intrachain disulfide bonds, and the many disulfide-rich proteins of the extracellular matrix and antibodies. In biotechnology and medicine, correct disulfide bond formation is important for the proper folding and stability of therapeutic proteins. Mispaired disulfides can lead to misfolding and aggregation. The cystine form refers to two cysteines linked by a disulfide bond.