Bacterial iron-sulfur cluster-containing and thiol-dependent enzymes (Fe-S/Thiol enzymes)

Bacterial enzymes containing iron-sulfur (Fe-S) clusters and thiol (-SH) groups are essential components of microbial metabolism, respiration, and DNA maintenance. These motifs are found in a wide array of proteins, including dehydratases like aconitase, which are critical for the tricarboxylic acid (TCA) cycle, and various oxidoreductases involved in electron transport (Source: Ezraty et al., 2017, Nature Reviews Microbiology). Because Fe-S clusters are highly sensitive to oxidative stress and chalcophilic metals, they serve as prime targets for antimicrobial agents. Drugs such as bismuth compounds, silver ions, and gallium work by displacing iron from these clusters or binding to the coordinating cysteine thiols, effectively poisoning the enzyme and leading to metabolic arrest (Source: Lemire et al., 2013, Nature Reviews Microbiology). This mechanism is particularly effective because it often hits multiple essential enzymes simultaneously, making it difficult for bacteria to develop resistance through single-point mutations (Source: Ge and Sun, 2007, Journal of Biological Inorganic Chemistry). For example, bismuth subsalicylate is known to inhibit the growth of Helicobacter pylori by targeting its urease and other thiol-dependent enzymes. Similarly, silver ions disrupt the respiratory chain by interacting with the Fe-S clusters of NADH dehydrogenase. However, the structural similarity between bacterial and human Fe-S clusters poses a challenge for achieving high therapeutic indices, necessitating careful drug design to target bacterial-specific pathways or uptake mechanisms. Overall, these enzymes represent a vulnerable Achilles' heel in bacterial physiology that can be exploited by diverse chemical classes.

Other names

Bacterial Fe-S cluster proteinsThiol-containing bacterial enzymesSulfhydryl-dependent bacterial enzymesIron-sulfur cluster-containing enzymes

Inhibition of enzymatic activity via metal displacement from Fe-S clusters or covalent modification of cysteine thiol groups.