Dihydrofolate Reductase (DHFR) is a key enzyme in cellular division as the final product of its enzymatic activity is Tetrahydrofolate (FH4) which contributes to the synthesis of thymidine and purines that are essential for nucleic acids synthesis. Thus, inhibitors of DHFR would decrease cellular multiplication which is the basis of cancer development and bacterial toxicity.
Methotrexate (MTX) drug is used as anti-cancer and Trimethoprim (TOP) as an anti-bacterial and many other inhibitors have been designed for different therapeutic purposes such as Pyrimethamine (PYR) which is used as an anti-malarial drug.
You're investigating the binding of the antimetabolites Methotrixate (MTX) and Trimethoprim (TOP). These compounds act as inhibitors of the Dihydrofolate Reductase enzyme (DHFR). They inhibit DHFR by competing at the site of binding against the natural substrate Folate (FOL) thereby binding strongly to the DHFR and preventing it from catalysis.
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Each of MTX and TOP ligands compete against the natural substrate of DHFR, folate (FOL). Start by examining the following:
FOL ligand chemistry (using MSD's ChemPDB)