Nucleotide-handling enzymes

Nucleotide-handling enzymes represent a broad and diverse functional class of proteins responsible for the synthesis, degradation, and interconversion of nucleotides, which serve as the fundamental building blocks of nucleic acids and as critical signaling molecules (Zimmermann, 2000). This category encompasses a wide range of enzymes, including DNA and RNA polymerases, kinases, nucleotidases, and helicases, all of which play essential roles in cellular processes such as DNA replication, transcription, and energy metabolism (Yegutkin, 2008). Because these enzymes are vital for the proliferation of both pathogens and cancer cells, they have long been exploited as primary therapeutic targets (Jordheim et al., 2013). For instance, many antiviral and anticancer drugs are nucleoside or nucleotide analogs that inhibit polymerases or act as chain terminators to halt replication (Galmarini et al., 2002). More recently, ectonucleotidases like CD39 and CD73 have emerged as significant targets in immuno-oncology due to their role in converting pro-inflammatory ATP into immunosuppressive adenosine within the tumor microenvironment (Allard et al., 2017). Despite their therapeutic utility, targeting these enzymes often presents challenges, such as potential off-target effects on host cellular machinery and the development of drug resistance.

Other names

Nucleotide-metabolizing enzymesNucleotide-processing enzymesPurinergic signaling enzymesEctonucleotidases

Inhibition of nucleic acid synthesis via chain termination or competitive inhibition, and modulation of extracellular purinergic signaling through the regulation of ATP and adenosine levels.