What is the function of dihydrofolate reductase?

Dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate to tetrahydrofolate (THF). THF is needed for the action of folate-dependent enzymes and is thus essential for DNA synthesis and methylation.

What is bacterial dihydrofolate reductase?

Dihydrofolate reductase catalyzes the reduction of dihy- drofolate with NADPH as the reducing substrate. This enzyme is of special interest because several of its inhibitors have been used in the treatment of neoplastic disease, malaria, bacterial infections, psoriasis, and other disorders (1).

Why is dihydrofolate reductase a drug target?

DHFR: the target Folate metabolism has long been recognized as an important and attractive target for chemotherapy because of its crucial role in the biosynthesis of nucleic-acid precursors.

What is DHFR and why is it important?

Dihydrofolate Reductase (DHFR) is a very important enzyme because it produces cofactors that are necessary for DNA synthesis. THF is an essential cofactor involved in the the transfer of methyl, methylene, and formyl groups from one molecule to another during the production of nucleotides and several amino acids.

How does the dihydrofolate reductase ( DHFR ) enzyme work?

From Wikipedia, the free encyclopedia Dihydrofolate reductase, or DHFR, is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as electron donor, which can be converted to the kinds of tetrahydrofolate cofactors used in 1-carbon transfer chemistry. In humans, the DHFR enzyme is encoded by the DHFR gene.

How is dihydrofolate reductase used in folic acid auxotrophs?

(3) In folic acid auxotrophs including animals and certain bacteria, the enzyme is used for converting nutritional folates such as dihydrofolate and folate into the coenzyme form, THF. Surprisingly, however, recent evidence showed that dihydrofolate reductase is not a universal enzyme.

What are the pH optima of dihydrofolate reductase?

In all tissues studied, the enzyme has two pH optima. Dihydrofolate reductase is inhibited by 0.01 μM aminopterin and amethopterin. It is possible to determine the concentration of folic acid antagonists in various tissues by titration with purified dihydrofolate reductase.

How is dihydrofolate reductase specified in E.coli?

A different type of dihydrofolate reductase is specified in E. coli by the folM gene; this protein is a member of the short-chain dehydrogenase reductase family. 115 An E. coli plasmid has been shown to specify a third dihydrofolate reductase type that has been interpreted as a primitive enzyme that has not undergone extensive evolution. 116