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Kinetic properties and inhibition of Trypanosoma cruzi 3‐hydroxy‐3‐methylglutaryl CoA reductase
Author(s) -
Hurtado-Guerrrero Ramón,
Peña-Dı́az Javier,
Montalvetti Andrea,
Ruiz-Pérez Luis M,
González-Pacanowska Dolores
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)03238-0
Subject(s) - reductase , enzyme , chemistry , coenzyme a , biochemistry , fluvastatin , anabolism , trypanosoma cruzi , biology , pharmacology , parasite hosting , world wide web , computer science , simvastatin
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.