Murray James B, Meroueh Samy O, Russell Rupert J M, Lentzen Georg, Haddad Jalal, Mobashery Shahriar
Vernalis (R&D), Ltd., Granta Park, Cambridge, UK.
Chem Biol. 2006 Feb;13(2):129-38. doi: 10.1016/j.chembiol.2005.11.004.
The X-ray crystal structures for the complexes of three designer antibiotics, compounds 1, 2, and 3, bound to two models for the ribosomal aminoacyl-tRNA site (A site) at 2.5-3.0 Angstroms resolution and that of neamine at 2.8 Angstroms resolution are described. Furthermore, the complex of antibiotic 1 bound to the A site in the entire 30S ribosomal subunit of Thermus thermophilus is reported at 3.8 Angstroms resolution. Molecular dynamics simulations revealed that the designer compounds provide additional stability to bases A1492 and A1493 in their extrahelical forms. Snapshots from the simulations were used for free energy calculations, which revealed that van der Waals and hydrophobic effects were the driving forces behind the binding of designer antibiotic 3 when compared to the parental neamine.
描述了三种设计型抗生素（化合物1、2和3）与核糖体氨酰基-tRNA位点（A位点）的两种模型结合的X射线晶体结构，分辨率为2.5 - 3.0埃，还描述了新霉素的晶体结构，分辨率为2.8埃。此外，还报道了抗生素1与嗜热栖热菌整个30S核糖体亚基中A位点结合的复合物，分辨率为3.8埃。分子动力学模拟表明，设计型化合物以其额外螺旋形式为碱基A1492和A1493提供了额外的稳定性。模拟的快照用于自由能计算，结果表明，与亲本新霉素相比，范德华力和疏水效应是设计型抗生素3结合的驱动力。
Zotero 插件