RT Journal Article SR Electronic T1 Reduced Nicotinamide Adenine Dinucleotide Phosphate-Dependent Binding of Competitive Inhibitors to Dihydrofolate Reductase JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 617 OP 620 VO 6 IS 6 A1 RALPH FREUDENTHAL A1 JEFFREY K. LOWE A1 PETER HEBBORN YR 1970 UL http://molpharm.aspetjournals.org/content/6/6/617.abstract AB 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.