Protein Structure-Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Braamfontein, Johannesburg, 2050, South Africa; Department of Medical Biochemistry, Alex Ekwueme Federal University Ndufu-Alike, Ebonyi State, Nigeria.
Protein Structure-Function and Research Unit, School of Molecular and Cell Biology, Faculty of Science, University of the Witwatersrand, Braamfontein, Johannesburg, 2050, South Africa.
Biochem Biophys Res Commun. 2024 Nov 19;734:150774. doi: 10.1016/j.bbrc.2024.150774. Epub 2024 Oct 1.
The dynamic and versatile group of enzymes referred to as glutathione S-transferases (GSTs) play diverse roles in cellular detoxification, safeguarding hosts from oxidative damage, and performing various other functions. This review explores different classes of GST, existence of polymorphisms in GST, functions of GST and utilizations of GST inhibitors in treatment of human diseases. The study indicates that the cytosolic GSTs, mitochondrial GSTs, microsomal GSTs, and bacterial proteins that provide resistance to Fosfomycin are the major classes. Given a GST, variation in its expression and function among individuals is due to the presence of polymorphic alleles that encode it. Genetic polymorphism might result in the modification of GST activity, thereby increasing individuals' vulnerability to harmful chemical compounds. GSTs have been demonstrated to play a regulatory function in cellular signalling pathways through kinases, S-Glutathionylation, and in detoxification processes. Various applications of bacterial GSTs and their potential roles in plants were examined. Targeting GSTs, especially GSTP1-1, is considered a potential therapeutic strategy for treating cancer and diseases linked to abnormal cell proliferation. Their role in cancer cell growth, differentiation, and resistance to anticancer agents makes them promising targets for drug development, offering prospects for the future.
被称为谷胱甘肽 S-转移酶(GSTs)的这组具有动态和多功能的酶在细胞解毒、保护宿主免受氧化损伤以及执行其他各种功能方面发挥着不同的作用。本综述探讨了 GST 的不同类别、GST 中的多态性的存在、GST 的功能以及 GST 抑制剂在人类疾病治疗中的应用。研究表明,细胞溶质 GSTs、线粒体 GSTs、微粒体 GSTs 和提供福司福霉素抗性的细菌蛋白是主要类别。对于给定的 GST,其在个体中的表达和功能的差异是由于存在编码它的多态性等位基因。遗传多态性可能导致 GST 活性的改变,从而增加个体对有害化合物的易感性。GSTs 已被证明通过激酶、S-谷胱甘肽化在细胞信号通路中发挥调节作用,并在解毒过程中发挥作用。还研究了细菌 GSTs 的各种应用及其在植物中的潜在作用。靶向 GSTs,特别是 GSTP1-1,被认为是治疗癌症和与异常细胞增殖相关疾病的潜在治疗策略。它们在癌细胞生长、分化和对抗癌药物的耐药性方面的作用使它们成为药物开发的有前途的靶点,为未来提供了前景。