Kinetic properties and inhibition of Trypanosoma cruzi 3‐hydroxy‐3‐methylglutaryl CoA reductase

FEBS Letters

Montalvetti, Andrea¹  Peña-Dı́az, Javier¹  Hurtado-Guerrrero, Ramón¹  González-Pacanowska, Dolores¹  Ruiz-Pérez, Luis M¹ 

[1] Instituto de Parasitologı́a y Biomedicina ‘López-Neyra’, Consejo Superior de Investigaciones Cientı́ficas, C/Ventanilla 11, 18001 Granada, Spain

关键词: 3-Hydroxy-3-methylglutaryl CoA reductase;    trypanosomatid;    Cross-linking;    Statin;    Ergosterol;    HMGR;    3-hydroxy-3-methylglutaryl CoA reductase;    HMG-CoA;    3-hydroxy-3-methylglutaryl CoA;   

DOI  :  10.1016/S0014-5793(01)03238-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown