Schuwirth Barbara S, Day J Michael, Hau Cathy W, Janssen Gary R, Dahlberg Albert E, Cate Jamie H Doudna, Vila-Sanjurjo Antón
Departments of Molecular and Cell Biology and Chemistry, University of California, Berkeley, California 94720, USA.
Nat Struct Mol Biol. 2006 Oct;13(10):879-86. doi: 10.1038/nsmb1150. Epub 2006 Sep 24.
The prokaryotic ribosome is an important target of antibiotic action. We determined the X-ray structure of the aminoglycoside kasugamycin (Ksg) in complex with the Escherichia coli 70S ribosome at 3.5-A resolution. The structure reveals that the drug binds within the messenger RNA channel of the 30S subunit between the universally conserved G926 and A794 nucleotides in 16S ribosomal RNA, which are sites of Ksg resistance. To our surprise, Ksg resistance mutations do not inhibit binding of the drug to the ribosome. The present structural and biochemical results indicate that inhibition by Ksg and Ksg resistance are closely linked to the structure of the mRNA at the junction of the peptidyl-tRNA and exit-tRNA sites (P and E sites).
原核生物核糖体是抗生素作用的重要靶点。我们测定了氨基糖苷类春日霉素（Ksg）与大肠杆菌70S核糖体复合物的X射线结构，分辨率为3.5埃。该结构表明，药物结合在30S亚基的信使RNA通道内，位于16S核糖体RNA中普遍保守的G926和A794核苷酸之间，这两个位点是Ksg耐药位点。令我们惊讶的是，Ksg耐药突变并不抑制药物与核糖体的结合。目前的结构和生化结果表明，Ksg的抑制作用和Ksg耐药性与肽基-tRNA和出位-tRNA位点（P和E位点）交界处的mRNA结构密切相关。
