Protein cysteine residue (Cys)

Protein cysteine residues are characterized by a reactive sulfhydryl (thiol) group that plays a pivotal role in protein structure, function, and regulation. They are essential for the formation of disulfide bridges, which stabilize the tertiary and quaternary structures of many extracellular and secreted proteins (Source: UniProt). Cysteines also function as potent nucleophiles in the catalytic sites of various enzymes, such as proteases and phosphatases, and act as ligands for metal ion coordination in zinc finger proteins (Source: PubMed, PMID: 23510398). Furthermore, the thiol group is highly sensitive to the cellular redox environment, undergoing reversible modifications like S-nitrosylation and S-glutathionylation that serve as key signaling mechanisms (Source: PubMed, PMID: 23415111). In drug discovery, specific cysteine residues are targeted by covalent inhibitors to achieve high selectivity and prolonged pharmacodynamics, as seen in treatments for various cancers (Source: PubMed, PMID: 21814247). However, the inherent reactivity of cysteines across the proteome necessitates careful design to avoid off-target effects and potential immunogenicity (Source: PubMed, PMID: 27033577).

Other names

Cysteine thiolSulfhydryl groupL-cysteine residueReactive cysteine

Covalent modification of the nucleophilic thiol group, typically via Michael addition with electrophilic warheads, to irreversibly or reversibly inhibit protein function (Source: PubMed, PMID: 21814247).