Makarov G I, Makarova T M
South Ural State University, Chelyabinsk, Russia, 454080.
Department of Chemistry, Lomonosov Moscow State University, Moscow, Russia, 119991.
J Comput Aided Mol Des. 2020 Mar;34(3):281-291. doi: 10.1007/s10822-019-00269-x. Epub 2019 Dec 12.
Linezolid, an antibiotic of oxazolidinone family, is a translation inhibitor. The mechanism of its action that consists in preventing the binding of aminoacyl-tRNA to the A-site of the large subunit of a ribosome was embraced on the basis of the X-ray structural analysis of the linezolid complexes with vacant bacterial ribosomes. However, the known structures of the linezolid complexes with bacterial ribosomes poorly explain the linezolid selectivity in suppression of protein biosynthesis, depending on the amino acid sequence of the nascent peptide. In the present study the most probable structure of the linezolid complex with a E. coli ribosome in the A,A/P,P-state that is in line with the results of biochemical studies of linezolid action has been obtained by molecular dynamics simulation methods.
利奈唑胺是一种恶唑烷酮类抗生素，是一种翻译抑制剂。其作用机制是阻止氨酰基tRNA与核糖体大亚基的A位点结合，这一机制是基于利奈唑胺与空的细菌核糖体复合物的X射线结构分析得出的。然而，利奈唑胺与细菌核糖体复合物的已知结构难以很好地解释利奈唑胺在抑制蛋白质生物合成方面的选择性，这种选择性取决于新生肽的氨基酸序列。在本研究中，通过分子动力学模拟方法获得了利奈唑胺与处于A,A/P,P状态的大肠杆菌核糖体复合物的最可能结构，该结构与利奈唑胺作用的生化研究结果一致。
