Dihydrofolate reductase (DHFR)

Dihydrofolate reductase is an essential enzyme that catalyzes the reduction of dihydrofolic acid to tetrahydrofolic acid using NADPH as an electron donor. This reaction is crucial for regenerating tetrahydrofolates required for the de novo synthesis of purines and thymidylates—key building blocks for DNA replication and cell division. Inhibition of DHFR leads to disruption in nucleotide biosynthesis and cell death, making it a validated therapeutic target in cancer chemotherapy (e.g., methotrexate) and antibacterial therapy (e.g., trimethoprim). The enzyme is highly conserved across species but exhibits structural differences between humans and bacteria that can be exploited pharmacologically[1][2][3][5]. Note on correctness ("is_incorrect"): The original target name "Dihydrofolate reductase and other folate-dependent enzymes involved in DNA synthesis" is overly broad. Only "Dihydrofolate reductase" should be considered the canonical form; "other folate-dependent enzymes" refers to a group rather than a specific molecular entity. For structured data purposes, this entry should focus solely on Dihydrofolate reductase as described above[1].

Other names

Tetrahydrofolate dehydrogenaseDHFRFolate reductase

Competitive inhibition of dihydrofolate binding site to block tetrahydrofolate production and disrupt DNA synthesis[2][5]