Dihydrofolate reductase (Staphylococcus aureus) (DHFR)

Dihydrofolate reductase (DHFR) from Staphylococcus aureus is a key enzyme in bacterial folate metabolism, catalyzing the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate. This reaction is essential for the de novo synthesis of purines, thymidylate (a DNA precursor), and methionine, making DHFR indispensable for bacterial growth and proliferation[1][5][6]. Because of its pivotal metabolic role, DHFR is a proven therapeutic target for antibacterial drugs such as trimethoprim[1][2][3][4]. Inhibition of S. aureus DHFR blocks nucleotide and amino acid synthesis, impeding cell division and survival. Drug resistance can arise via chromosomal mutations or acquisition of alternative DHFR isoforms, especially in methicillin-resistant Staphylococcus aureus (MRSA), greatly complicating treatment and driving efforts to develop new inhibitors with activity against resistant DHFR variants[1][4].

Other names

FolAsaDHFRDHFR (when contextually referring to Staphylococcus aureus)

Competitive inhibition of DHFR active site, blocking reduction of dihydrofolate to tetrahydrofolate, thereby inhibiting DNA and amino acid synthesis[1][2][3]. Resultant cytostatic and bactericidal effects due to impaired nucleotide and methionine biosynthesis