Escherichia coli dihydrofolate reductase (EcDHFR) (EcDHFR)

Escherichia coli dihydrofolate reductase (EcDHFR) is a critical enzyme in the bacterial folate biosynthetic pathway, responsible for the NADPH-dependent reduction of 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate (UniProt: P0ABQ4). This enzymatic activity is essential for the production of tetrahydrofolate derivatives required for the synthesis of thymidylate, purines, and several amino acids, which are indispensable for DNA replication and bacterial growth (PubMed: 15590603). As a well-established therapeutic target, EcDHFR is inhibited by antifolate drugs such as trimethoprim, which binds to the bacterial enzyme with significantly higher affinity than to the human homolog, ensuring selective antimicrobial action (StatPearls: NBK513239). The inhibition of EcDHFR leads to a depletion of the intracellular folate pool, resulting in the arrest of nucleic acid synthesis and bacteriostatic effects. However, the clinical efficacy of EcDHFR inhibitors is frequently compromised by the development of resistance, primarily through point mutations in the folA gene that alter the drug-binding site (PubMed: 25135932). Beyond its clinical relevance, EcDHFR serves as a primary model system in structural biology and enzymology for studying protein-ligand interactions and enzyme catalysis (PubMed: 10640675).

Other names

DHFRfolA5,6,7,8-tetrahydrofolate:NADP+ oxidoreductaseDihydrofolate reductase

Competitive inhibition of the enzyme dihydrofolate reductase, which prevents the reduction of dihydrofolate to tetrahydrofolate, thereby halting the synthesis of essential nucleic acids and proteins.