DHFR, short for dihydrofolate reductase, is an essential enzyme found in various organisms, including bacteria, fungi, plants, and animals, serving a crucial role in cellular metabolism. This enzyme catalyzes the conversion of dihydrofolate (DHF) to tetrahydrofolate (THF), an active form of folate, by reducing NADPH (nicotinamide adenine dinucleotide phosphate) as an electron donor.
THF is a vital cofactor in numerous biological processes, such as DNA synthesis, amino acid metabolism, and nucleotide synthesis, making DHFR an important player in these cellular activities. The conversion of DHF to THF is required to generate one-carbon units necessary for the synthesis of purines, thymidylic acid, methionine, and the methylation of DNA.
In medical applications, DHFR inhibitors are commonly utilized as chemotherapeutic agents to target rapidly dividing cancer cells, as the inhibition of DHFR activity hampers the production of THF and subsequently disrupts DNA synthesis and cell replication. Consequently, these inhibitors are employed in the treatment of various cancers, including leukemia, ovarian, breast, and lung cancer.
Understanding the structure and mechanism of DHFR has paved the way for the development of pharmaceuticals that can selectively inhibit the enzyme's activity, thereby offering potential therapeutic applications. Furthermore, studying the mechanisms of DHFR in microbial organisms has contributed to the development of antibiotic drugs targeting bacterial DHFRs, aiding in the treatment of bacterial infections.
