Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.
Nat Struct Mol Biol. 2010 Mar;17(3):289-93. doi: 10.1038/nsmb.1755. Epub 2010 Feb 14.
Viomycin and capreomycin belong to the tuberactinomycin family of antibiotics, which are among the most effective antibiotics against multidrug-resistant tuberculosis. Here we present two crystal structures of the 70S ribosome in complex with three tRNAs and bound to either viomycin or capreomycin at 3.3- and 3.5-A resolution, respectively. Both antibiotics bind to the same site on the ribosome, which lies at the interface between helix 44 of the small ribosomal subunit and helix 69 of the large ribosomal subunit. The structures of these complexes suggest that the tuberactinomycins inhibit translocation by stabilizing the tRNA in the A site in the pretranslocation state. In addition, these structures show that the tuberactinomycins bind adjacent to the binding sites for the paromomycin and hygromycin B antibiotics, which may enable the development of new derivatives of tuberactinomycins that are effective against drug-resistant strains.
威米拉霉素和卷曲霉素属于放线菌素类抗生素，是治疗耐多药结核分枝杆菌最有效的抗生素之一。本文报道了分别以 3.3 和 3.5 Å分辨率解析的 70S 核糖体与三个 tRNA 复合物及与威米拉霉素或卷曲霉素复合物的两个晶体结构。两种抗生素均结合在核糖体的同一部位，该部位位于小亚基 44 号螺旋和大亚基 69 号螺旋之间的连接处。这些复合物的结构表明，放线菌素类抗生素通过稳定预移位状态的 A 位 tRNA 来抑制转位。此外，这些结构表明，放线菌素类抗生素与巴龙霉素和潮霉素 B 抗生素的结合位点相邻，这可能使开发针对耐药菌株有效的新型放线菌素类抗生素衍生物成为可能。
