Abstract：
Glyoxalase II, the second of 2 enzymes in the glyoxalase system, is a hydroxyacylglutathione hydrolase that catalyses the hydrolysis of S-d-lactoylglutathione to form d-lactic acid and glutathione, which is released from the active site. The tripeptide glutathione is the major sulfhydryl antioxidant and has been shown to control several functions, including S-glutathionylation of proteins. S-Glutathionylation is a way for the cells to store reduced glutathione during oxidative stress, or to protect protein thiol groups from irreversible oxidation, and few enzymes involved in protein S-glutathionylation have been found to date. In this work, the enzyme glyoxalase II and its substrate S-d-lactoylglutathione were incubated with malate dehydrogenase or with actin, resulting in a glutathionylation reaction. Glyoxalase II was also submitted to docking studies. Computational data presented a high propensity of the enzyme to interact with malate dehydrogenase or actin through its catalytic site and further in silico investigation showed a high folding stability of glyoxalase II toward its own reaction product glutathione both protonated and unprotonated. This study suggests that glyoxalase II, through a specific interaction of its catalytic site with target proteins, could be able to perform a rapid and specific protein S-glutathionylation using its natural substrate S-d-lactoylglutathione.
CONCLUSIONS: This article reports for the first time a possible additional role of Glo2 that, after interacting with a target protein, is able to promote S-glutathionylation using its natural substrate SLG, a glutathione derived compound. In this perspective, Glo2 can play a new important regulatory role inS-glutathionylation, acquiring further significance in cellular post-translational modifications of proteins.
CONCLUSIONS: This article reports for the first time a possible additional role of Glo2 that, after interacting with a target protein, is able to promote S-glutathionylation using its natural substrate SLG, a glutathione derived compound. In this perspective, Glo2 can play a new important regulatory role inS-glutathionylation, acquiring further significance in cellular post-translational modifications of proteins.
摘要：
乙二醛酶II，乙二醛酶系统中两种酶中的第二种，是一种羟基酰基谷胱甘肽水解酶，催化S-d-乳酰基谷胱甘肽水解形成d-乳酸和谷胱甘肽，从活性位点释放。三肽谷胱甘肽是主要的巯基抗氧化剂，并已被证明可以控制多种功能，包括蛋白质的S-谷胱甘肽酰化。S-谷胱甘肽是细胞在氧化应激过程中储存还原型谷胱甘肽的一种方式，或保护蛋白质巯基不可逆氧化，迄今为止，很少发现与蛋白质S-谷胱甘肽酰化有关的酶。在这项工作中,将乙二醛酶II及其底物S-d-乳酰基谷胱甘肽与苹果酸脱氢酶或肌动蛋白一起孵育，导致谷胱甘肽酰化反应。乙二醛酶II也被提交到对接研究。计算数据显示，该酶通过其催化位点与苹果酸脱氢酶或肌动蛋白相互作用的倾向很高，进一步的计算机研究表明，乙二醛酶II对其自身的反应产物谷胱甘肽具有很高的折叠稳定性，两者都是质子化和未质子化的。这项研究表明，乙二醛酶II，通过其催化位点与靶蛋白的特定相互作用，能够使用其天然底物S-d-乳酰谷胱甘肽进行快速且特异性的蛋白质S-谷胱甘肽化。
结论：本文首次报道了Glo2可能的其他作用，在与靶蛋白相互作用后，能够使用其天然底物SLG促进S-谷胱甘肽酰化，谷胱甘肽衍生的化合物。从这个角度来看,Glo2可以在S-谷胱甘肽磷酸化中发挥新的重要调节作用，在蛋白质的细胞翻译后修饰中获得进一步的意义。
结论：本文首次报道了Glo2可能的其他作用，在与靶蛋白相互作用后，能够使用其天然底物SLG促进S-谷胱甘肽酰化，谷胱甘肽衍生的化合物。从这个角度来看,Glo2可以在S-谷胱甘肽磷酸化中发挥新的重要调节作用，在蛋白质的细胞翻译后修饰中获得进一步的意义。
