cysteines

Cysteine is a sulfur-containing amino acid that is one of the 20 standard amino acids used to build proteins. Its side chain features a thiol group (-SH) that can form covalent disulfide bonds with another cysteine, linking polypeptides or stabilizing folded proteins. When two cysteines are linked by a disulfide bond, the pair is termed cystine.

Cysteine can be synthesized in the human body from methionine through the transsulfuration pathway, making it a nonessential, but conditionally required, amino acid. Diets rich in methionine, cysteine, or protein commonly supply adequate cysteine. It is especially important in infants and in certain disease states where synthesis may be insufficient.

The thiol group has a pKa of about 8.3, so at physiological pH a fraction exists as the thiolate anion and is highly reactive. Cysteine residues act as nucleophiles in enzyme active sites (for example in cysteine proteases) and participate broadly in redox biology through thiol-disulfide exchange. Cysteines are easily oxidized to various sulfenic, sulfinic, and sulfonic acids, influencing protein function and signaling. Post-translational modifications such as S-nitrosylation, S-glutathionylation, and palmitoylation regulate protein activity and localization.

In proteins, cysteines form disulfide bonds that stabilize tertiary and quaternary structures, especially in extracellular environments. Cystine, the oxidized dimer of two cysteine residues, is common in secreted and structural proteins. Cysteine residues also coordinate metal ions in motifs such as zinc fingers.