title: Kinetic properties and inhibition of Trypanosoma cruzi 3-hydroxy-3-methylglutaryl CoA reductase.
abstract: A detailed kinetic analysis of the recombinant soluble enzyme 3-hydroxy-3-methylglutaryl CoA reductase (HMGR) from Trypanosoma cruzi has been performed. The enzyme catalyzes the normal anabolic reaction and the reductant is NADPH. It also catalyzes the oxidation of mevalonate but at a lower proportion compared to the anabolic reaction. We report that the catalytically active species of HMGR in solution is the tetrameric form. Fluvastatin inhibited competitively the enzyme while cerivastatin binds by a mechanism which is more accurately described by a biphasic process characteristic of a class of 'slow, tight-binding' inhibitors.
authors.affiliation: Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, C/Ventanilla 11, 18001 Granada, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Hurtado-Guerrrero
authors.forename: Javier
authors.initials: J
authors.lastname: Peña-Díaz
authors.forename: Andrea
authors.initials: A
authors.lastname: Montalvetti
authors.forename: Luis M
authors.initials: LM
authors.lastname: Ruiz-Pérez
authors.forename: Dolores
authors.initials: D
authors.lastname: González-Pacanowska
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002384:Catalysis / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism / Q000494:pharmacology; D000077340:Fluvastatin; D006903:Hydroxymethylglutaryl CoA Reductases / Q000737:chemistry* / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008798:Mevalonic Acid / Q000737:chemistry; D009249:NADP / Q000737:chemistry; D010084:Oxidation-Reduction / Q000187:drug effects; D020836:Protein Structure, Quaternary; D011725:Pyridines / Q000378:metabolism / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000201:enzymology*
chemical_list: D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D011725:Pyridines; D000077340:Fluvastatin; D009249:NADP; C086276:cerivastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D008798:Mevalonic Acid