Polyethylene Sulfonate: A Tight-Binding Inhibitor of 6-Phosphogluconate Dehydrogenase ofCryptococcus neoformans

Polyethylene sulfonate (PES) or polyvinyl sulfonate was found to be a potent inhibitor of a number of fungal enzymes, including 6-phosphogluconate dehydrogenase fromCryptococcus neoformans.The inhibition was apparently competitive versus either NADP or 6-phosphogluconate, with 50% inhibition at PES concentrations below 10 nM. Replots of slopes of double-reciprocal plots versus inhibitor concentration were sharply concave upward, whereas replots of slope versus [PES]3were linear. The inhibition was freely reversible upon dilution of the enzyme–PES complex. A model is presented that involves initial binding of the long (Mr50,000) polyanionic PES at a remote site on the enzyme, followed by interaction of the end of the tethered polymer with the binding site for NADP or for 6-phosphogluconate.