Laboratory of Reproductive Biology, Institute of Biotechnology of the Czech Academy of Sciences, Prumyslova 595, 25250 Vestec, Czech Republic.
Laboratory for Biology of Secondary Metabolism, Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic.
Int J Biol Macromol. 2022 Oct 31;219:1360-1371. doi: 10.1016/j.ijbiomac.2022.07.192. Epub 2022 Aug 3.
Toxin-antitoxin (TA) systems are small genetic elements which encode toxin proteins that interfere with vital cellular functions. PepA1 and PepG1 toxin proteins, known also as SprA1 and SprG1, are type I TA. In Staphylococcus aureus (S. aureus), their expression without the antitoxin counterparts (SprA1 and SprF1), is lethal to the pathogen. Molecular Dynamics (MD) simulation was performed for PepA1 and PepG1 to understand their dynamic state, conformational changes, and their toxicity. The protein structures were constructed and used for MD simulation and the conformational changes, stability, flexibility, fluctuations, hydrophobicity, and role of their dynamic state on function prediction were studied extensively by GROMACS MD simulation analysis tools. In silico study indicated that the PepA1 and PepG1 proteins change their structural conformation from an open to closed state where PepA1 conformational changes were faster (10 ns) than PepG1 (20 ns) while PepG1 exerted more stability and flexibility than PepA1. According to SASA values, PepG1 is more hydrophobic than the PepA1 and forms fewer hydrogen bonds than PepA1. The in vivo study with PepA1 and PepG1 proteins provided evidence that both the conformation changes between the open and closed states and the amino acid sequence are crucial for peptide toxicity.
毒素-抗毒素 (TA) 系统是编码毒素蛋白的小型遗传元件，这些毒素蛋白会干扰重要的细胞功能。PepA1 和 PepG1 毒素蛋白，也称为 SprA1 和 SprG1，是 I 型 TA。在金黄色葡萄球菌（S. aureus）中，没有对应的抗毒素（SprA1 和 SprF1）表达时，它们的表达对病原体是致命的。进行了分子动力学（MD）模拟，以了解 PepA1 和 PepG1 的动态状态、构象变化及其毒性。构建了蛋白质结构，并将其用于 MD 模拟，使用 GROMACS MD 模拟分析工具广泛研究了构象变化、稳定性、灵活性、波动、疏水性以及它们的动态状态对功能预测的作用。计算机研究表明，PepA1 和 PepG1 蛋白的结构构象从开放状态转变为闭合状态，其中 PepA1 的构象变化（10ns）快于 PepG1（20ns），而 PepG1 比 PepA1 更稳定和灵活。根据 SASA 值，PepG1 比 PepA1 更疏水，形成的氢键比 PepA1 少。PepA1 和 PepG1 蛋白的体内研究表明，开放和闭合状态之间的构象变化以及氨基酸序列对于肽毒性至关重要。
