C 末端螺旋的微小修饰改变了θ类谷胱甘肽转移酶 T1-1 催化的优选化学反应。
Minor modifications of the C-terminal helix reschedule the favored chemical reactions catalyzed by theta class glutathione transferase T1-1.
机构信息
Department of Biochemistry and Organic Chemistry, Uppsala University, Biomedical Center, Box 576, SE-75123 Uppsala, Sweden.
出版信息
J Biol Chem. 2010 Feb 19;285(8):5639-45. doi: 10.1074/jbc.M109.074757. Epub 2009 Dec 18.
Abstract
Adaptive responses to novel toxic challenges provide selective advantages to organisms in evolution. Glutathione transferases (GSTs) play a pivotal role in the cellular defense because they are main contributors to the inactivation of genotoxic compounds of exogenous as well as of endogenous origins. GSTs are promiscuous enzymes catalyzing a variety of chemical reactions with numerous alternative substrates. Despite broad substrate acceptance, individual GSTs display pronounced selectivities such that only a limited number of substrates are transformed with high catalytic efficiency. The present study shows that minor structural changes in the C-terminal helix of mouse GST T1-1 induce major changes in the substrate-activity profile of the enzyme to favor novel chemical reactions and to suppress other reactions catalyzed by the parental enzyme.
摘要
对新的毒性挑战的适应反应为生物进化提供了选择性优势。谷胱甘肽转移酶（GSTs）在细胞防御中起着关键作用，因为它们是使外源性和内源性遗传毒性化合物失活的主要贡献者。GSTs 是一种具有多种化学活性的多功能酶，可以催化多种化学反应，具有许多替代底物。尽管具有广泛的底物接受能力，但个别 GSTs 显示出明显的选择性，使得只有有限数量的底物以高催化效率转化。本研究表明，小鼠 GST T1-1 的 C 端螺旋的微小结构变化会导致酶的底物-活性谱发生重大变化，有利于新的化学反应，并抑制亲本酶催化的其他反应。
相似文献
1
Minor modifications of the C-terminal helix reschedule the favored chemical reactions catalyzed by theta class glutathione transferase T1-1.C 末端螺旋的微小修饰改变了θ类谷胱甘肽转移酶 T1-1 催化的优选化学反应。
J Biol Chem. 2010 Feb 19;285(8):5639-45. doi: 10.1074/jbc.M109.074757. Epub 2009 Dec 18.
2
An ensemble of theta class glutathione transferases with novel catalytic properties generated by stochastic recombination of fragments of two mammalian enzymes.通过两种哺乳动物酶片段的随机重组产生的具有新型催化特性的θ类谷胱甘肽转移酶集合。
J Mol Biol. 2002 Apr 19;318(1):59-70. doi: 10.1016/S0022-2836(02)00032-3.
3
Structural determinants of glutathione transferases with azathioprine activity identified by DNA shuffling of alpha class members.通过α类成员的DNA改组鉴定出具有硫唑嘌呤活性的谷胱甘肽转移酶的结构决定因素。
J Mol Biol. 2008 Feb 1;375(5):1365-79. doi: 10.1016/j.jmb.2007.11.034. Epub 2007 Nov 19.
4
Residue 234 is a master switch of the alternative-substrate activity profile of human and rodent theta class glutathione transferase T1-1.残基234是人和啮齿动物θ类谷胱甘肽转移酶T1-1的替代底物活性谱的主开关。
Biochim Biophys Acta. 2010 Apr;1800(4):466-73. doi: 10.1016/j.bbagen.2010.01.003. Epub 2010 Jan 25.
5
Human glutathione transferase A4-4 crystal structures and mutagenesis reveal the basis of high catalytic efficiency with toxic lipid peroxidation products.人谷胱甘肽转移酶A4-4的晶体结构与诱变研究揭示了其对有毒脂质过氧化产物具有高催化效率的基础。
J Mol Biol. 1999 May 7;288(3):427-39. doi: 10.1006/jmbi.1999.2697.
6
Molecular evolution of Theta-class glutathione transferase for enhanced activity with the anticancer drug 1,3-bis-(2-chloroethyl)-1-nitrosourea and other alkylating agents.Theta 类谷胱甘肽转移酶的分子进化以提高与抗癌药物 1,3-双-(2-氯乙基)-1-亚硝脲和其他烷化剂的活性。
Arch Biochem Biophys. 2010 May;497(1-2):28-34. doi: 10.1016/j.abb.2010.03.001. Epub 2010 Mar 4.
7
Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily.谷胱甘肽转移酶的结构、功能与进化：对一个古老酶超家族非哺乳动物成员分类的启示
Biochem J. 2001 Nov 15;360(Pt 1):1-16. doi: 10.1042/0264-6021:3600001.
8
Human theta class glutathione transferase: the crystal structure reveals a sulfate-binding pocket within a buried active site.人θ类谷胱甘肽转移酶：晶体结构揭示了一个埋藏活性位点内的硫酸盐结合口袋。
Structure. 1998 Mar 15;6(3):309-22. doi: 10.1016/s0969-2126(98)00034-3.
9
Emergence of a novel highly specific and catalytically efficient enzyme from a naturally promiscuous glutathione transferase.从一种天然具有多催化活性的谷胱甘肽转移酶中产生一种新型的高特异性和催化效率的酶。
Biochim Biophys Acta. 2008 Dec;1780(12):1458-63. doi: 10.1016/j.bbagen.2008.07.007. Epub 2008 Jul 28.
10
Involvement of the carboxyl groups of glutathione in the catalytic mechanism of human glutathione transferase A1-1.谷胱甘肽的羧基在人谷胱甘肽转移酶A1-1催化机制中的作用。
Biochemistry. 1996 Jun 18;35(24):7731-42. doi: 10.1021/bi9601619.
引用本文的文献
1
Effects of Substrate-Binding Site Residues on the Biochemical Properties of a Tau Class Glutathione -Transferase from .底物结合位点残基对. 中的 Tau 类谷胱甘肽转移酶的生化特性的影响。
Genes (Basel). 2019 Dec 24;11(1):25. doi: 10.3390/genes11010025.
2
Exploring sequence-function space of a poplar glutathione transferase using designed information-rich gene variants.利用设计的信息丰富的基因变体探索杨树谷胱甘肽转移酶的序列-功能空间。
Protein Eng Des Sel. 2017 Aug 1;30(8):543-549. doi: 10.1093/protein/gzx045.
3
Glutathione-binding site of a bombyx mori theta-class glutathione transferase.家蚕θ类谷胱甘肽转移酶的谷胱甘肽结合位点
PLoS One. 2014 May 21;9(5):e97740. doi: 10.1371/journal.pone.0097740. eCollection 2014.
4
Genetic variations in human glutathione transferase enzymes: significance for pharmacology and toxicology.人类谷胱甘肽转移酶的基因变异：对药理学和毒理学的意义
Hum Genomics Proteomics. 2010 Jun 13;2010:876940. doi: 10.4061/2010/876940.
5
Molecular evolution and the role of oxidative stress in the expansion and functional diversification of cytosolic glutathione transferases.分子进化与氧化应激在胞质谷胱甘肽转移酶扩张和功能多样化中的作用。
BMC Evol Biol. 2010 Sep 15;10:281. doi: 10.1186/1471-2148-10-281.
6
Metabolism of isothiocyanates in individuals with positive and null GSTT1 and M1 genotypes after drinking watercress juice.十字花科蔬菜汁摄入后 GSTT1 和 M1 基因型阳性和阴性个体中异硫氰酸酯的代谢。
Clin Nutr. 2010 Dec;29(6):813-8. doi: 10.1016/j.clnu.2010.06.010. Epub 2010 Jul 24.
本文引用的文献
1
Identification of emerging quasi-species in directed enzyme evolution.定向酶进化中新兴准种的鉴定。
Biochemistry. 2009 Oct 13;48(40):9330-9. doi: 10.1021/bi901168q.
2
Linkage disequilibrium between two high-frequency deletion polymorphisms: implications for association studies involving the glutathione-S transferase (GST) genes.两个高频缺失多态性之间的连锁不平衡：对涉及谷胱甘肽-S转移酶（GST）基因的关联研究的影响。
PLoS Genet. 2009 May;5(5):e1000472. doi: 10.1371/journal.pgen.1000472. Epub 2009 May 8.
3
Enzyme (re)design: lessons from natural evolution and computation.酶（重新）设计：来自自然进化与计算的经验教训。
Curr Opin Chem Biol. 2009 Feb;13(1):10-8. doi: 10.1016/j.cbpa.2009.01.014. Epub 2009 Feb 23.
4
The origin, evolution and structure of the protein world.蛋白质世界的起源、演化与结构。
Biochem J. 2009 Feb 1;417(3):621-37. doi: 10.1042/BJ20082063.
5
MODBASE, a database of annotated comparative protein structure models and associated resources.MODBASE，一个带注释的比较蛋白质结构模型及相关资源的数据库。
Nucleic Acids Res. 2009 Jan;37(Database issue):D347-54. doi: 10.1093/nar/gkn791. Epub 2008 Oct 23.
6
The molecular basis of host adaptation in cactophilic Drosophila: molecular evolution of a glutathione S-transferase gene (GstD1) in Drosophila mojavensis.嗜仙人掌果蝇宿主适应性的分子基础：莫哈韦果蝇中谷胱甘肽S-转移酶基因（GstD1）的分子进化
Genetics. 2008 Feb;178(2):1073-83. doi: 10.1534/genetics.107.083287. Epub 2008 Feb 1.
7
Novel class of glutathione transferases from cyanobacteria exhibit high catalytic activities towards naturally occurring isothiocyanates.来自蓝细菌的新型谷胱甘肽转移酶对天然存在的异硫氰酸酯具有高催化活性。
Biochem J. 2007 Aug 15;406(1):115-23. doi: 10.1042/BJ20070328.
8
The evolution of catalytic efficiency and substrate promiscuity in human theta class 1-1 glutathione transferase.人类θ类1-1谷胱甘肽转移酶催化效率和底物选择性的演变
J Mol Biol. 2006 Dec 1;364(3):400-10. doi: 10.1016/j.jmb.2006.09.012. Epub 2006 Sep 9.
9
Structural basis for ligand promiscuity in cytochrome P450 3A4.细胞色素P450 3A4中配体混杂性的结构基础。
Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13682-7. doi: 10.1073/pnas.0603236103. Epub 2006 Sep 5.
10
Tools for integrated sequence-structure analysis with UCSF Chimera.用于与UCSF Chimera进行综合序列-结构分析的工具。
BMC Bioinformatics. 2006 Jul 12;7:339. doi: 10.1186/1471-2105-7-339.
Zotero 插件