Lynch S R, Puglisi J D
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305-5126, USA.
J Mol Biol. 2001 Mar 9;306(5):1023-35. doi: 10.1006/jmbi.2000.4419.
The aminoglycoside antibiotics target a region of highly conserved nucleotides in the aminoacyl-tRNA site (A site) of 16 S RNA on the 30 S subunit. The structures of a prokaryotic decoding region A-site oligonucleotide free in solution and bound to the aminoglycosides paromomycin and gentamicin C1A have been determined. Here, the structure of a eukaryotic decoding region A-site oligonucleotide has been determined using homonuclear and heteronuclear NMR spectroscopy, and compared to the unbound prokaryotic rRNA structure. The two structures are similar, with a U1406-U1495 base-pair, a C1407-G1494 Watson-Crick base-pair, and a G1408-A1493 base-pair instead of the A1408-A1493 base-pair of the prokaryotic structure. The two structures differ in the orientation of the 1408 position with respect to A1493; G1408 is rotated toward the major groove, which is the binding pocket for aminoglycosides. The structures also differ in the stacking geometry of G1494 on A1493, which could have slight long-range conformational effects.
氨基糖苷类抗生素作用于30S亚基上16S RNA的氨酰tRNA位点（A位点）中高度保守的核苷酸区域。已确定了溶液中游离的原核生物解码区A位点寡核苷酸以及与氨基糖苷类药物巴龙霉素和庆大霉素C1A结合后的结构。在此，利用同核和异核核磁共振光谱法确定了真核生物解码区A位点寡核苷酸的结构，并与未结合的原核生物rRNA结构进行了比较。这两种结构相似，存在一个U1406-U1495碱基对、一个C1407-G1494沃森-克里克碱基对以及一个G1408-A1493碱基对，而非原核生物结构中的A1408-A1493碱基对。这两种结构在1408位置相对于A1493的取向上有所不同；G1408向大沟旋转，大沟是氨基糖苷类药物的结合口袋。这两种结构在G1494在A1493上的堆积几何形状上也存在差异，这可能会产生轻微的长程构象效应。
