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

被引：20

作者：

Hurtado-Guerrrero, R ^{[1
]}

Peña-Díaz, J ^{[1
]}

Montalvetti, A ^{[1
]}

Ruiz-Pérez, LM ^{[1
]}

González-Pecanowska, D ^{[1
]}

机构：

[1] CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 08001, Spain

来源：

FEBS LETTERS | 2002年 / 510卷 / 03期

关键词：

3-hydroxy-3-methylglutaryl CoA reductase; trypanosomatid; cross-linking; statin; ergosterol;

D O I：

10.1016/S0014-5793(01)03238-0

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

引用

页码：141 / 144

页数：4

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