Microbial metal-dependent enzymes and metalloproteins

Microbial metal-dependent enzymes and metalloproteins represent a diverse and essential class of proteins in bacteria, fungi, and protozoa that utilize metal ions—such as zinc, iron, manganese, and nickel—as cofactors for catalytic activity or structural stability (Frontiers in Pharmacology, 2021). These proteins are involved in a wide array of fundamental biological processes, including DNA synthesis, metabolic pathways, and the neutralization of reactive oxygen species (MDPI, 2024). In pathogenic microbes, metalloenzymes often function as critical virulence factors or mediate resistance to conventional antibiotics, exemplified by the zinc-dependent metallo-beta-lactamases (e.g., NDM-1) that confer resistance to carbapenems (ACS Chemical Reviews, 2018). Therapeutic strategies targeting this class include the use of small-molecule inhibitors that coordinate with the active-site metal, metal chelators that disrupt metal homeostasis, and siderophore-drug conjugates that exploit microbial metal acquisition systems (NIH, 2024). However, a significant challenge in drug development is achieving selectivity to avoid off-target inhibition of essential human metalloenzymes, such as matrix metalloproteinases or carbonic anhydrases (Frontiers in Chemistry, 2021).

Other names

Microbial metalloenzymesBacterial metalloproteinsMetal-dependent microbial proteinsMicrobial metal-binding proteins

Inhibition of catalytic activity through active-site metal coordination, competitive inhibition, metal chelation, or exploitation of metal transport systems (e.g., siderophore-drug conjugates).