Department of Bioinformatics, Fraunhofer-Institute for Algorithms and Scientific Computing (SCAI), Schloss Birlinghoven, 53754 Sankt Augustin, Germany.
Bioorg Med Chem. 2012 Dec 15;20(24):7194-205. doi: 10.1016/j.bmc.2012.09.025. Epub 2012 Sep 22.
The thiostrepton antibiotic inhibits bacterial protein synthesis by binding to a cleft formed by the ribosomal protein L11 and 23S's rRNA helices 43-44 on the 70S ribosome. It was proposed from crystal structures that the ligand restricts L11's N-terminal movement and thus prevents proper translation factor binding. An exact understanding of thiostrepton's impact on the binding site's dynamics at atomistic resolution is still missing. Here we report an all-atom molecular dynamics simulations of the binary L11·rRNA and the ternary L11·rRNA·thiostrepton complex (rRNA = helices 43-44). We demonstrate that thiostrepton directly impacts the binding site's atomic and biomacromolecular dynamics.
硫链丝菌素抗生素通过与核糖体蛋白 L11 和 23S rRNA 螺旋 43-44 形成的裂隙结合来抑制细菌蛋白质合成。根据晶体结构，该配体限制了 L11 的 N 端运动，从而阻止了适当的翻译因子结合。然而，对于硫链丝菌素对原子分辨率结合位点动力学的影响，目前仍缺乏确切的了解。在这里，我们报告了二元 L11·rRNA 和三元 L11·rRNA·硫链丝菌素复合物（rRNA = 螺旋 43-44）的全原子分子动力学模拟。我们证明了硫链丝菌素直接影响结合位点的原子和生物大分子动力学。
