Glutathione S-transferases--a review.
Glutathione S-transferases--a review.
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DOI：
10.2174/0929867306666220208213032
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发表时间：
1999-04
影响因子：
4.1
通讯作者：
Anna E. Salinas;M. Wong
中科院分区：
文献类型：
--
作者：
Anna E. Salinas;M. Wong
谷胱甘肽s -转移酶（GSTs）形成一组多基因同工酶，参与细胞解毒的外源性和内源性化合物。gst被分为几个子类，alpha, mu， pi和theta。根据序列相似性和免疫交叉反应性进行分类。gst对GSH表现出高水平的特异性，但亲电性第二底物在两类之间和类内可能存在显著差异，尽管它们的序列相似。x射线晶体学和定点诱变研究共同阐明了GSTs的结构和机制。催化作用通过与谷胱甘肽（GSH）结合发生，毒性较低且亲水性较强的产物随后可部分代谢并排出体外。然而，这种宝贵的服务在化疗期间是不利的，因为GSTs与肿瘤细胞的多药耐药有关。不同GSTs亚型的表达水平是组织特异性的。正常细胞和肿瘤细胞之间表达的差异是令人感兴趣的，在大多数情况下，gst的水平增加，特别是p-GST。要了解gst在耐药性中的复杂作用，首先要确定各异构体的表达模式和底物特异性。在化疗期间，使用同工酶特异性GSH类似物作为抑制剂来调节GST活性是对抗癌症的一种有前途的策略。这篇综述试图提供一个详细的文献综述，涉及不同类别的gst，它们的功能和机制，以及gst作为疾病治疗靶点的使用，目前在提交时。
The Glutathione S-transferases (GSTs) form a group of multi-gene isoenzymes involved in the cellular detoxification of both xenobiotic and endobiotic compounds. GSTs have been divided into a number of subclasses, alpha, mu, pi, and theta. The classification was made on the basis of sequence similarity and immunological cross-reactivity. GSTs show a high level of specificity toward GSH but the electrophilic second substrate can vary significantly both between and within the classes in spite of their sequence similarity. X-ray crystallography and site-directed mutagenesis studies have together elucidated the structure and mechanism of GSTs. Catalysis occurs by conjugation with glutathione (GSH) and the less toxic and more hydrophilic products can then be partially metabolised and excreted. This invaluable service is however disadvantageous during chemotherapy where GSTs have been associated with multi-drug resistance of tumour cells. Levels of expression of different isoforms of GSTs are tissue specific. The variations in expression between normal and tumour cells are of interest and in most cases the levels of GSTs are increased, especially p-GST. Understanding the complex role that GSTs play in drug resistance begins with determining the pattern of isoform expression and the substrate specificities of each isoform. The use of isozyme-specific, GSH analogues as inhibitors to modulate GST activity during chemotherapy is a promising strategy in the battle against cancer. This review attempts to provide a detailed overview of the literature concerning the different classes of GSTs, their function and mechanism and the use of GSTs as therapeutic targets for disease as current at the time of submission.