Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
J Mol Model. 2013 Aug;19(8):3143-51. doi: 10.1007/s00894-013-1848-2. Epub 2013 Apr 25.
The transcriptional repressor Rex plays key roles in modulating respiratory gene expression. It senses the redox poise of the NAD(H) pool. Rex from Streptomyces rimosus (Sr-Rex) is a newly identified protein. Its structure and complex with substrates are not determined yet. In this study, the three-dimensional (3D) structural models of Sr-Rex dimer and its complex with cofactors were constructed by homology modeling. The stability of the constructed Sr-Rex models and the detailed interactions between Sr-Rex and cofactors were further investigated by molecular dynamics simulations. The results demonstrated that the conformation of Sr-Rex changed a lot when binding with the reduced NADH or oxidized NAD(+). Once binding with NADH, the Sr-Rex dimer displayed an opener conformation, which would weaken the interaction of Sr-Rex with Rex operator DNA (ROP). Key residues responsible for the binding were then identified. The computational results were consistent with experimental results, and hence provided insights into the molecular mechanism of Sr-Rex binding with ROP and NADH/NAD(+), which might be helpful for the development of biosensor.
转录抑制剂 Rex 在调节呼吸基因表达方面起着关键作用。它能感知 NAD(H) 池的氧化还原状态。来自嗜热链霉菌（Streptomyces rimosus）的 Rex（Sr-Rex）是一种新鉴定的蛋白质。其结构及其与底物的复合物尚未确定。在这项研究中，通过同源建模构建了 Sr-Rex 二聚体及其与辅因子复合物的三维（3D）结构模型。通过分子动力学模拟进一步研究了构建的 Sr-Rex 模型的稳定性以及 Sr-Rex 与辅因子之间的详细相互作用。结果表明，Sr-Rex 与还原型 NADH 或氧化型 NAD(+) 结合时构象发生了很大变化。一旦与 NADH 结合，Sr-Rex 二聚体呈现出开放构象，这会削弱 Sr-Rex 与 Rex 操纵子 DNA（ROP）的相互作用。然后确定了负责结合的关键残基。计算结果与实验结果一致，从而深入了解了 Sr-Rex 与 ROP 和 NADH/NAD(+) 结合的分子机制，这可能有助于生物传感器的开发。
