Microbial metalloenzymes involved in DNA replication and related processes

Microbial metalloenzymes involved in DNA replication and related processes constitute a broad functional class of proteins that require metal ions—such as magnesium, zinc, iron, or manganese—as essential cofactors for their catalytic activity or structural stability (Source: UniProt; Nature Reviews Microbiology). This group includes critical enzymes such as ribonucleotide reductases (RNR), which catalyze the rate-limiting step in deoxyribonucleotide synthesis, as well as DNA polymerases, primases, and topoisomerases responsible for genome duplication and maintenance (Source: Journal of Biological Chemistry). These enzymes are fundamental to the survival and proliferation of bacterial, viral, and fungal pathogens, making them significant targets for anti-infective drug development (Source: PubMed, PMID: 25658227). For example, the drug hydroxyurea inhibits RNR by disrupting its metal-dependent tyrosyl radical, while foscarnet targets the metal-binding site of viral DNA polymerases to halt replication (Source: StatPearls). A major challenge in targeting these enzymes is the structural similarity between microbial and human metalloenzymes, which can lead to off-target effects and host toxicity (Source: NIH, National Institute of Allergy and Infectious Diseases).

Other names

Microbial DNA replication metalloenzymesBacterial metallo-nucleasesMetallo-polymerasesMetallo-topoisomerasesMicrobial DNA metabolism metalloenzymes

These enzymes utilize metal ion cofactors (e.g., Mg2+, Zn2+, Fe, Mn) to facilitate phosphoryl transfer, stabilize transition states, or generate catalytic radicals; drugs inhibit them by chelating these metal centers, mimicking pyrophosphate, or blocking the active site (Source: Nature Reviews Microbiology; Annual Review of Biochemistry).