TY - JOUR T1 - Reduced Nicotinamide Adenine Dinucleotide Phosphate-Dependent Binding of Competitive Inhibitors to Dihydrofolate Reductase JF - Molecular Pharmacology JO - Mol Pharmacol SP - 617 LP - 620 VL - 6 IS - 6 AU - RALPH FREUDENTHAL AU - JEFFREY K. LOWE AU - PETER HEBBORN Y1 - 1970/11/01 UR - http://molpharm.aspetjournals.org/content/6/6/617.abstract N2 - The enzyme dihydrofolate reductase (EC 1.5.1.3), which catalyzes the reduced pyridine nucleotide-dependent reduction of dihydrofolate to tetrahydrofolate, is inhibited by 6-N-ω-(N-ethyl-N-2-chloroethyl)propyl-2,4,6-triamino-5-(dichlorophenylazo)pyrimidines acting as active site-directed irreversible inhibitors. A requirement for the binding of these inhibitors to the enzyme prior to alkylation is the presence of NADPH. Apparently the binding of NADPH to the enzyme causes a conformational change in the protein that makes the substrate-binding site accessible to either the substrate or a competitive inhibitor. ER -