The structures of antibiotics bound to the E site region of the 50 S ribosomal subunit of Haloarcula marismortui: 13-deoxytedanolide and girodazole.
The structures of antibiotics bound to the E site region of the 50 S ribosomal subunit of Haloarcula marismortui: 13-deoxytedanolide and girodazole.
复制标题
与 Haloarcula marismortui 50 S 核糖体亚基 E 位点区域结合的抗生素结构：13-脱氧特那内酯和吉罗达唑。
DOI：
10.1016/j.jmb.2007.01.081
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发表时间：
2007
影响因子：
5.6
通讯作者：
Moore,PeterB
中科院分区：
文献类型：
--
作者：
Schroeder,SusanJ;Blaha,Gregor;Tirado-Rives,Julian;Steitz,ThomasA;Moore,PeterB
海洋嗜盐藻(Haloarcula Marismortui)的50个S核糖体亚基与两种抗生素的络合物的晶体结构确定了抗生素与核糖体相互作用并抑制蛋白质合成的新位点。13-脱氧萜内酯与50 S亚基的E位结合，与tRNACCA位于同一位置，从而抑制蛋白质合成，与脱酰化的tRNA竞争E位结合。吉罗达唑结合在E位点区附近，但在一定程度上被掩埋，并可能通过干扰E位点处发生的构象变化来抑制tRNA结合。13-脱氧戊内酯对真核核糖体的特异性是由于它与L44E蛋白的广泛相互作用，而L44E蛋白是古生物和真核核糖体的E位组分，而不是真细菌核糖体的E位组分。此外，真细菌E位点所特有的L28蛋白与13-脱氧萜内酯所占据的位置重叠，排除了其与真细菌核糖体的结合。吉罗达唑是真核生物和古细菌所特有的，因为它与L15发生了真细菌不可能发生的相互作用。
Crystal structures of the 50 S ribosomal subunit from Haloarcula marismortui complexed with two antibiotics have identified new sites at which antibiotics interact with the ribosome and inhibit protein synthesis. 13-Deoxytedanolide binds to the E site of the 50 S subunit at the same location as the CCA of tRNA, and thus appears to inhibit protein synthesis by competing with deacylated tRNAs for E site binding. Girodazole binds near the E site region, but is somewhat buried and may inhibit tRNA binding by interfering with conformational changes that occur at the E site. The specificity of 13-deoxytedanolide for eukaryotic ribosomes is explained by its extensive interactions with protein L44e, which is an E site component of archaeal and eukaryotic ribosomes, but not of eubacterial ribosomes. In addition, protein L28, which is unique to the eubacterial E site, overlaps the site occupied by 13-deoxytedanolide, precluding its binding to eubacterial ribosomes. Girodazole is specific for eukarytes and archaea because it makes interactions with L15 that are not possible in eubacteria.