disulfide bond

Meaning: A disulfide bond is a covalent bond between the sulfur atoms of two cysteine side chains. The cysteines can be far apart in the primary sequence and meet only after folding, so the bond stabilizes tertiary structure. It can also link separate chains, adding to quaternary structure. It forms in oxidizing surroundings such as the endoplasmic reticulum lumen and the extracellular space, and is uncommon in the reducing cytosol. Two linked cysteines are called cystine. Insulin and antibodies are examples.

Equation: 2 R–SH ⇌ R–S–S–R + 2H⁺ + 2e⁻, where R–SH is a cysteine thiol side chain, R–S–S–R is the disulfide, H⁺ is a proton and e⁻ is an electron (charge −1.60 × 10⁻¹⁹ C). Forward is oxidation; reverse is reduction.

On the MCAT: A reducing agent such as β-mercaptoethanol or DTT breaks disulfide bonds and can unfold a protein, while urea or heat mainly disrupt noncovalent interactions. In SDS-PAGE, a protein of two chains joined by a disulfide runs as one band without a reducing agent and as two bands with it.

Common confusion: It is not a peptide bond and is not part of the backbone; it joins side chains. Methionine contains sulfur but cannot form one. Forming the bond is oxidation, not reduction.