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Dihydrofolate Reductase (Bacterial) (DHFR)

Target: DHFR
Molecular classification: Enzyme

Overview

Dihydrofolate reductase (DHFR) is an essential enzyme found in bacteria that catalyzes the reduction of 7,8-dihydrofolate (DHF) to 5,6,7,8-tetrahydrofolate (THF), using NADPH. It is crucial for maintaining cellular pools of THF, which are required for the synthesis of purines and thymidylate for DNA and RNA synthesis. Inhibition of bacterial DHFR is a validated antibacterial strategy.

Mechanism of action

Inhibition of bacterial dihydrofolate reductase, leading to depletion of tetrahydrofolates and cessation of DNA synthesis.

Biological functions

Nucleotide biosynthesisDNA replicationCell division

Disease associations

Infection

Safety considerations

Potential for off-target effects due to structural similarity to mammalian DHFRDevelopment of drug resistance through mutations or acquisition of alternative DHFR genes

Interacting drugs

Trimethoprim

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