Center for Innovation Competence (ZIK) plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Straße 2, 17489, Greifswald, Germany.
Institute of Anatomy and Cell Biology, University Medicine Greifswald, Friedrich-Loeffler-Straße 23c, Greifswald, 17487, Germany.
Chemistry. 2021 Oct 21;27(59):14702-14710. doi: 10.1002/chem.202102306. Epub 2021 Sep 15.
Several studies have revealed that various diseases such as cancer have been associated with elevated phospholipase A (PLA ) activity. Therefore, the regulation of PLA catalytic activity is undoubtedly vital. In this study, effective inactivation of PLA due to reactive species produced from cold physical plasma as a source to model oxidative stress is reported. We found singlet oxygen to be the most relevant active agent in PLA inhibition. A more detailed analysis of the plasma-treated PLA identified tryptophan 128 as a hot spot, rich in double oxidation. The significant dioxidation of this interfacial tryptophan resulted in an N-formylkynurenine product via the oxidative opening of the tryptophan indole ring. Molecular dynamics simulation indicated that the efficient interactions between the tryptophan residue and phospholipids are eliminated following tryptophan dioxidation. As interfacial tryptophan residues are predominantly involved in the attaching of membrane enzymes to the bilayers, tryptophan dioxidation and indole ring opening leads to the loss of essential interactions for enzyme binding and, consequently, enzyme inactivation.
已有多项研究表明，多种疾病（如癌症）与磷脂酶 A（PLA）活性升高有关。因此，PLA 催化活性的调节无疑至关重要。本研究报告了利用冷等离子体作为模型氧化应激源产生的活性物质来有效失活 PLA。我们发现单线态氧是 PLA 抑制中最相关的活性物质。对经等离子体处理的 PLA 的更详细分析确定色氨酸 128 为热点，富含双氧化。该界面色氨酸的显著双氧化导致通过色氨酸吲哚环的氧化打开生成 N-甲酰犬尿氨酸产物。分子动力学模拟表明，色氨酸双氧化后，色氨酸残基与磷脂之间的有效相互作用被消除。由于界面色氨酸残基主要参与膜酶与双层的附着，因此色氨酸双氧化和吲哚环打开导致酶结合的必需相互作用丧失，从而导致酶失活。
