title: Polyethylene sulfonate: a tight-binding inhibitor of 6-phosphogluconate dehydrogenase of Cryptococcus neoformans.
abstract: Polyethylene sulfonate (PES) or polyvinyl sulfonate was found to be a potent inhibitor of a number of fungal enzymes, including 6-phosphogluconate dehydrogenase from Cryptococcus 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]3 were linear. The inhibition was freely reversible upon dilution of the enzyme-PES complex. A model is presented that involves initial binding of the long (M(r) 50,000) 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.
authors.affiliation: Department of Biochemistry and Anaerobic Microbiology, Virginia Polytechnic Institute and State University, Blacksburg 24061-0308, USA.
authors.forename: W G
authors.initials: WG
authors.lastname: Niehaus
authors.forename: R H
authors.initials: RH
authors.lastname: White
authors.forename: S B
authors.initials: SB
authors.lastname: Richardson
authors.forename: A
authors.initials: A
authors.lastname: Bourne
authors.forename: W K
authors.initials: WK
authors.lastname: Ray
mesh_terms: D017738:Alkanesulfonic Acids / Q000737:chemistry*; D002021:Buffers; D003455:Cryptococcus neoformans / Q000201:enzymology*; D004340:Drug Contamination; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004795:Enzyme Stability; D005942:Gluconates / Q000378:metabolism; D008970:Molecular Weight; D009025:Morpholines / Q000737:chemistry*; D009249:NADP / Q000378:metabolism; D010734:Phosphogluconate Dehydrogenase / Q000037:antagonists & inhibitors*; D011145:Polyvinyls / Q000494:pharmacology*; D013451:Sulfonic Acids / Q000494:pharmacology*
chemical_list: D017738:Alkanesulfonic Acids; D002021:Buffers; D004791:Enzyme Inhibitors; D005942:Gluconates; D009025:Morpholines; D011145:Polyvinyls; D013451:Sulfonic Acids; C008959:lyapolate; C004550:2-(N-morpholino)ethanesulfonic acid; D009249:NADP; D010734:Phosphogluconate Dehydrogenase; C008884:6-phosphogluconic acid