Dihydrofolate reductase type 2 (DHFR type II)

Type II dihydrofolate reductase (R67 DHFR) is a plasmid-encoded bacterial enzyme that reduces dihydrofolic acid to tetrahydrofolic acid using NADPH as an electron donor[2]. It is structurally distinct from the chromosomally encoded Type I DHFR: R67 DHFR forms a symmetric homotetramer with a central pore serving as the active site. This target is notable primarily for mediating bacterial resistance to antifolate drugs such as trimethoprim. Unlike human DHFR, R67 DHFR lacks conventional substrate and cofactor binding sites, relying instead on a distinctive "molecular clamp" for catalysis. Its presence poses major challenges for antibiotic therapy, as it allows bacteria to evade standard DHFR-targeted drugs by horizontal gene transfer of plasmids encoding this enzyme[2].

Other names

R67 dihydrofolate reductaseType II dihydrofolate reductasePlasmid-encoded dihydrofolate reductase

Competitive inhibition of enzyme active site (by drugs like trimethoprim)\nPrevention of tetrahydrofolate formation, inhibiting DNA and RNA synthesis in microbes