DNA and tRNA-Asp methyltransferase PfDNMT2 (PfDNMT2)

DNA and tRNA-Asp methyltransferase PfDNMT2 is a critical enzyme in the malaria-causing parasite Plasmodium falciparum, belonging to the highly conserved DNMT2 family. Unlike traditional DNA methyltransferases, PfDNMT2 primarily functions as a multisubstrate methyltransferase that catalyzes the methylation of cytosine 38 in the anticodon loop of tRNA-Asp, while also exhibiting low-level DNA cytosine-5 methylation activity. This enzyme plays a vital role in the parasite's life cycle by regulating protein synthesis and contributing to the epigenetic landscape, which is essential for the parasite's adaptation to environmental stress within the host. Because PfDNMT2 is the only identifiable DNA methyltransferase homolog in the Plasmodium genome, it has emerged as a significant therapeutic target for antimalarial drug development. Inhibitors such as azanucleosides have shown the ability to disrupt parasite growth by interfering with these methylation processes. However, achieving high selectivity for the parasite enzyme over human homologs remains a primary challenge in drug design.

Other names

Plasmodium falciparum DNA methyltransferase 2tRNA aspartic acid methyltransferase 1TRDMT1PfTRDMT1C-5 cytosine-specific DNA methyltransferase

Inhibition of cytosine-5 methyltransferase activity through covalent binding or competitive inhibition of the S-adenosyl-L-methionine binding site.