Bacterial thiol-containing enzymes

Bacterial thiol-containing enzymes are a diverse class of proteins that utilize the nucleophilic sulfhydryl (-SH) group of cysteine residues for catalytic activity, structural integrity, or redox regulation. These enzymes are essential for fundamental bacterial processes, including central metabolism (e.g., glyceraldehyde-3-phosphate dehydrogenase), cellular respiration (e.g., succinate dehydrogenase), and the maintenance of redox balance through systems like thioredoxin and glutathione. Furthermore, specific thiol-containing enzymes such as metallo-beta-lactamases (e.g., NDM-1) are major drivers of antibiotic resistance in Gram-negative pathogens by hydrolyzing carbapenems and other beta-lactam antibiotics. Due to the high affinity of thiols for soft metal ions and electrophiles, these enzymes are the primary targets for antimicrobial agents like silver ions, mercury-based compounds, and novel inhibitors like ebselen. Interaction with these agents typically results in the covalent modification of the active-site thiol, leading to irreversible enzyme inactivation, disruption of the respiratory chain, and the induction of lethal oxidative stress. However, therapeutic application is often limited by a lack of selectivity over human thiol-dependent enzymes and the potential for neutralization by host thiols in the systemic environment.

Other names

Bacterial sulfhydryl-containing enzymesCysteine-dependent bacterial enzymesBacterial thiol-dependent enzymesBacterial thiol-dependent antioxidant systems

Covalent inhibition of sulfhydryl groups; Zinc chelation in metallo-beta-lactamases; Disruption of bacterial redox homeostasis; Inhibition of the respiratory chain; Induction of reactive oxygen species (ROS)