Sulfhydryl-containing enzymes involved in protein and DNA synthesis (SH-enzymes)

Sulfhydryl-containing enzymes involved in protein and DNA synthesis represent a broad functional category of proteins that utilize the reactive thiol (-SH) group of cysteine residues for catalytic activity, structural stability, or regulation. This group includes essential enzymes such as ribonucleotide reductase, which is fundamental for deoxyribonucleotide production, as well as various DNA polymerases and aminoacyl-tRNA synthetases required for genetic replication and translation (Source: PubChem, NIH). Historically, these enzymes have served as the primary pharmacological targets for heavy metal-based therapeutic agents and antiseptics, including organic mercurials like thimerosal and arsenicals like melarsoprol. These compounds exert their effects by forming stable covalent mercaptide bonds with the enzyme's sulfhydryl groups, leading to irreversible inhibition of enzymatic function and subsequent cell death (Source: StatPearls). While effective against certain pathogens and cancer cells, the lack of specificity for microbial versus host enzymes often results in significant systemic toxicity, particularly neurotoxicity and nephrotoxicity (Source: PubMed). Consequently, modern drug development typically focuses on more selective inhibitors of specific individual enzymes within this class to improve the therapeutic index.

Other names

Thiol-dependent enzymesCysteine-dependent enzymesSulfhydryl-dependent enzymesSH-group containing enzymes

Covalent inhibition of enzyme activity through the formation of mercaptide bonds with essential cysteine sulfhydryl groups, disrupting catalytic sites and protein folding.