Farnesyl pyrophosphate synthase: a key enzyme in isoprenoid biosynthetic pathway and potential molecular target for drug development
Farnesyl pyrophosphate synthase: a key enzyme in isoprenoid biosynthetic pathway and potential molecular target for drug development
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DOI：
10.1016/j.nbt.2012.07.001
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发表时间：
2013-01-25
影响因子：
5.4
通讯作者：
Kaul, Sanjana
中科院分区：
文献类型：
--
作者：
Dhar, Manoj K.;Koul, Archana;Kaul, Sanjana
近年来，类异戊二烯生物合成途径越来越受到人们的重视，利用分子生物学方法研究了类异戊二烯生物合成途径中的关键酶及其在细胞代谢中的作用。该途径中的关键酶是法尼基焦磷酸（EC 2.5.1.10）合酶（FPPS），其为必需类异戊二烯如类胡萝卜素、睡茄内酯、泛醌、长萜醇、甾醇等的生物合成提供前体，并且还有助于蛋白质的法尼基化和香叶基化。它是一种链延长酶，催化两个异戊烯基二磷酸分子与二甲基烯丙基二磷酸的头尾缩合形成焦磷酸法呢酯（FPP）。最近的研究已经验证了FPPS作为双膦酸盐药物开发的分子靶点，用于抗肿瘤以及人类病原体。本文综述了FPPS酶的特性、结构和功能关系、进化、定位以及作为药物开发靶点的研究进展。
As isoprenoid biosynthetic pathway has gained importance since last few years, key enzymes of this pathway have been characterized and their functional roles in the cell metabolism have been explored using molecular biology approaches. A key enzyme in this pathway is farnesyl pyrophosphate (EC 2.5.1.10) synthase (FPPS) which supplies precursors for the biosynthesis of essential isoprenoids like carotenoids, withanolides, ubiquinones, dolichols, sterols, among others and also helps in farnesylation and geranylation of proteins. It is a chain elongation enzyme which catalyzes head to tail condensation of two molecules of isopentenyl diphosphate with dimethylallyl diphosphate to form farnesyl pyrophosphate (FPP). Recent studies have validated FPPS as a molecular target of bisphosphonates for drug development against tumors as well as human pathogens. The present paper synthesizes the information on characterization, structural and functional relationships, evolution, localization as well as advances on FPPS enzyme as a target for drug development.