Multiple microbial metalloproteins and enzymes

Multiple microbial metalloproteins and enzymes refers to a diverse set of bacterial proteins that require metal ions, such as nickel, iron, or zinc, for their biological activity and structural integrity [1, 3]. This target is primarily associated with the pharmacological action of bismuth-containing compounds used to treat gastrointestinal disorders and infections [1, 5]. Key enzymes within this group include urease, which is essential for Helicobacter pylori to neutralize stomach acid, as well as various dehydrogenases and proteases involved in microbial respiration and energy metabolism [3, 4]. Bismuth ions (Bi3+) exert their antimicrobial effect by displacing native metal cofactors from these enzymes or by forming high-affinity bonds with essential thiol groups on cysteine residues, leading to irreversible enzyme inhibition [3, 4]. This broad-spectrum inhibition disrupts the bacterial cell wall, interferes with ATP production, and prevents bacterial adherence to the gastric epithelium [2, 5]. Because these drugs target multiple essential pathways simultaneously, they are highly effective against antibiotic-resistant strains and exhibit a low frequency of acquired resistance [4, 5]. [1] DrugBank Online. Bismuth subsalicylate. drugbank.com. [2] PubChem. Bismuth subsalicylate. pubchem.ncbi.nlm.nih.gov. [3] Sun, H., et al. (2004). Bismuth-based drugs: the role of metalloprotein interactions. Journal of Inorganic Biochemistry. [4] Ge, R., & Sun, H. (2007). Bioinorganic chemistry of bismuth and antimony: target sites of metallodrugs. Dalton Transactions. [5] Marshall, B. J. (1991). Mechanism of action of bismuth in the treatment of Helicobacter pylori. Alimentary Pharmacology & Therapeutics.

Other names

Microbial metalloenzymesBacterial metalloproteinsBismuth-binding microbial proteinsH. pylori metalloenzymes

Inhibition of enzyme activity via displacement of essential metal ions or binding to functional thiol groups