Kinetic properties and inhibition of Trypanosoma cruzi 3-hydroxy-3-methylglutaryl CoA reductase |
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Authors: | Ramn Hurtado-Guerrrero Javier Pea-Díaz Andrea Montalvetti Luis M Ruiz-Prez Dolores Gonzlez-Pacanowska |
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Institution: | Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, C/Ventanilla 11, 18001 Granada, Spain. |
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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. |
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Keywords: | 3-Hydroxy-3-methylglutaryl CoA reductase trypanosomatid Cross-linking Statin Ergosterol |
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