Thiol-containing enzyme

Thiol-containing enzymes are a broad functional class of proteins that utilize the sulfhydryl (-SH) group of a cysteine residue for catalytic activity, structural stability, or regulatory sensing (Source: Nature Reviews Drug Discovery, 2021). This category encompasses several critical enzyme families, including cysteine proteases such as cathepsins and caspases, oxidoreductases like thioredoxin reductase, and various metabolic enzymes (Source: StatPearls, 2023). The high nucleophilicity of the cysteine thiol makes these enzymes susceptible to covalent modification, a property exploited by numerous drugs to achieve potent and often irreversible inhibition (Source: PubMed, 2022). For instance, the antiviral drug nirmatrelvir targets the main protease of SARS-CoV-2, while disulfiram inhibits aldehyde dehydrogenase by reacting with its active-site thiol (Source: PubChem). Despite their therapeutic potential in treating cancer, viral infections, and inflammatory disorders, thiol-containing enzymes present significant drug design challenges due to the risk of off-target reactivity with other cysteine-rich proteins or cellular antioxidants like glutathione (Source: NIH). Consequently, developing highly selective inhibitors is essential to minimize toxicity and idiosyncratic adverse effects associated with broad thiol reactivity.

Other names

Cysteine-dependent enzymeSulfhydryl-containing enzymeCysteine enzymeCysteine-based enzyme

Covalent inhibition of the catalytic cysteine residue through electrophilic attack on the thiol group, leading to irreversible or slowly reversible enzyme inactivation (Source: Nature Reviews Drug Discovery).