What is the function of dihydrofolate reductase?
Dihydrofolate reductase is a small enzyme that plays a supporting role, but an essential role, in the building of DNA and other processes. It manages the state of folate, a snaky organic molecule that shuttles carbon atoms to enzymes that need them in their reactions.
Do humans have dihydrofolate reductase?
In humans, the DHFR enzyme is encoded by the DHFR gene. It is found in the q11→q22 region of chromosome 5. Bacterial species possess distinct DHFR enzymes (based on their pattern of binding diaminoheterocyclic molecules), but mammalian DHFRs are highly similar.
What is the molecular weight of DHFR?
24 kDa
The molecular weight of the His-Tag DHFR protein, as resolved on a denaturing SDS gel, is 24 kDa.
Which reaction directly produces dihydrofolate?
The physiological function of dihydrofolate reductase (DHFR) is the reduction of 7,8-dihydrofolate (7,8-DHF) (1) produced in the reaction of thymidylate synthase and possibly by autooxidation of tetrahydrofolate.
What drugs inhibit dihydrofolate reductase?
5.1 Classical DHFR Inhibitors. The two main classical DHFR inhibitors are aminopterin (AM) and methotrexate (MTX, amethopterin), which were designed by replacing an enol-type OH group at C-4 of the natural substrate (DHF) by an amino group.
How does trimethoprim inhibit dihydrofolate reductase?
Mechanism of Action Trimethoprim is 50,000 to 100,000 times more active against bacterial dihydrofolate reductase than against the human enzyme. Trimethoprim interferes with the conversion of dihydrofolate to tetrahydrofolate, the precursor of folinic acid and ultimately of purine and DNA synthesis (Fig. 33-3).
What inhibits bacterial dihydrofolate reductase?
Pyrimethamine and trimethoprim are the most widely used dihydrofolate reductase inhibitors. Pyrimethamine is a known terattogen but is more effective then trimethoprim, which is usually administered in conjunction with a dihydropteroate synthase inhibitor (sulfamethoxazole).
What reaction does DHFR catalyze include the reactants and products?
Dihydrofolate reductase (DHFR) catalyzes the NADPH-dependent reduction of dihydrofolate (DHF), yielding tetrahydrofolate (THF), an important reaction in the folate cycle, which supplies one-carbon units for the biosynthesis of deoxythymidine monophosphate (dTMP), and for reactions involved in the biosynthesis of …
What type of inhibitor is trimethoprim?
Trimethoprim is a selective inhibitor of parasitic and bacterial dihydrofolate reductase.
