假尿苷修饰影响氨基糖苷类药物与细菌核糖体69螺旋的结合。
Pseudouridine modifications influence binding of aminoglycosides to helix 69 of bacterial ribosomes.
作者信息
Sakakibara Yogo, Chow Christine S
机构信息
Department of Chemistry, Wayne State University, Detroit, MI 48202, USA.
出版信息
Org Biomol Chem. 2017 Oct 18;15(40):8535-8543. doi: 10.1039/c7ob02147j.
Development of antibiotics that target new regions of functionality is a possible way to overcome antibiotic resistance. In this study, the interactions of aminoglycoside antibiotics with helix 69 of the E. coli 23S rRNA in the context of complete 70S ribosomes or the isolated 50S subunit were investigated by using chemical probing and footprinting analysis. Helix 69 is a dynamic RNA motif that plays major roles in bacterial ribosome activity. Neomycin, paromomycin, and gentamicin interact with the stem region of helix 69 in complete 70S ribosomes, but have diminished binding to the isolated 50S subunit. Pseudouridine modifications in helix 69 were shown to impact the aminoglycoside interactions. These results suggest a requirement for a specific conformational state of helix 69 for efficient aminoglycoside binding, and imply that this motif may be a suitable target for mechanism-based therapeutics.
开发针对新功能区域的抗生素是克服抗生素耐药性的一种可能途径。在本研究中，通过化学探针和足迹分析，研究了氨基糖苷类抗生素与完整70S核糖体或分离的50S亚基背景下大肠杆菌23S rRNA螺旋69的相互作用。螺旋69是一个动态RNA基序，在细菌核糖体活性中起主要作用。新霉素、巴龙霉素和庆大霉素在完整的70S核糖体中与螺旋69的茎区相互作用，但与分离的50S亚基的结合减弱。结果表明，螺旋69中的假尿苷修饰会影响氨基糖苷类药物的相互作用。这些结果表明，螺旋69需要特定的构象状态才能有效结合氨基糖苷类药物，这意味着该基序可能是基于机制的治疗的合适靶点。
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