Cysteine-containing proteins and enzymes

Cysteine-containing proteins and enzymes represent a vast and diverse group of biological molecules characterized by the presence of the sulfur-containing amino acid cysteine. Cysteine residues are uniquely reactive due to their nucleophilic thiol group, which allows them to participate in catalytic mechanisms, metal coordination, and the formation of stabilizing disulfide bonds [1.2.1, 1.3.1]. In the context of pharmacology, these proteins are critical components of the cellular "thiolstat," a redox-sensitive signaling network that regulates processes such as apoptosis, inflammation, and gene expression [1.2.3]. Many modern therapeutic strategies involve the design of covalent inhibitors that target specific, often non-conserved, cysteine residues to achieve high potency and prolonged duration of action [1.3.1]. Notable examples include kinase inhibitors like ibrutinib and osimertinib, as well as anti-inflammatory agents like dimethyl fumarate [1.3.2]. However, the high reactivity of the cysteine proteome also poses significant safety challenges, as non-selective modification of these proteins can lead to off-target toxicity, immunogenicity, and cellular stress [1.3.2, 1.3.4]. Consequently, achieving selectivity for a specific cysteine residue within the broader "cysteine proteome" is a primary goal in covalent drug discovery [1.3.1].

Other names

Cysteine proteomeThiol-containing proteinsRedox-sensitive proteinsCysteine-rich proteinsThiolstat components

Covalent inhibition of specific cysteine residues, redox modulation of the cellular thiolstat, and S-alkylation or S-nitrosylation of reactive thiols [1.3.1, 1.3.2].