Sulfhydryl-containing enzyme

Sulfhydryl-containing enzymes are a diverse group of proteins that utilize the nucleophilic properties of the cysteine thiol (-SH) group for catalysis, regulation, or structural integrity. This broad category includes critical therapeutic targets such as cysteine proteases (e.g., cathepsins and caspases), which are involved in protein degradation and apoptosis, and metabolic enzymes like aldehyde dehydrogenase (ALDH) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) [1][2]. The reactivity of the sulfhydryl group makes these enzymes susceptible to modulation by various pharmacological agents, including covalent inhibitors and redox-active compounds. For instance, the drug disulfiram exerts its effects by covalently modifying the active-site thiol of ALDH, while arsenic trioxide targets the thiol-rich active sites of thioredoxin reductase to induce apoptosis in cancer cells [3][4]. Historically, these enzymes have also been recognized as the primary targets of heavy metal toxicity, where ions like mercury and lead bind to essential thiols, disrupting cellular metabolism [5]. While targeting specific sulfhydryl-containing enzymes offers significant therapeutic potential in oncology and inflammatory diseases, the ubiquity of cysteine residues across the proteome presents challenges for achieving high selectivity and minimizing off-target toxicity [6]. Sources: [1] Turk, V., et al. (2012). "Cysteine cathepsins: from structure to function and clinical applications." Biochimica et Biophysica Acta. [2] Cooper, A. J., et al. (2011). "The importance of sulfhydryl groups in mitochondrial function." Journal of Bioenergetics and Biomembranes. [3] Koppaka, V., et al. (2012). "Aldehyde dehydrogenase inhibitors: a comprehensive review." Pharmacological Reviews. [4] Lu, J., & Holmgren, A. (2007). "Thioredoxin reductase as a target for anticancer drugs." Free Radical Biology and Medicine. [5] Valko, M., et al. (2005). "Metals, toxicity and oxidative stress." Current Medicinal Chemistry. [6] Conte, M. L., & Carroll, K. S. (2013). "The chemistry of thiol oxidation and detection." ACS Chemical Biology.

Other names

Thiol-containing enzymeCysteine-dependent enzymeThiol enzymeSulfhydryl-dependent enzyme

Covalent modification, oxidation, or metal-binding of the active-site cysteine thiol group, leading to enzyme inactivation.