THIOLATION OF URIDINE CARBON-2 RESTRICTS THE MOTIONAL DYNAMICS OF THE TRANSFER-RNA WOBBLE POSITION NUCLEOSIDE
THIOLATION OF URIDINE CARBON-2 RESTRICTS THE MOTIONAL DYNAMICS OF THE TRANSFER-RNA WOBBLE POSITION NUCLEOSIDE
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DOI：
10.1021/ja00033a044
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发表时间：
1992-03-25
影响因子：
15
通讯作者：
NAWROT, B
中科院分区：
文献类型：
--
作者：
AGRIS, PF;SIERZPUTOWSKAGRACZ, H;NAWROT, B
转移RNA摆动位置尿苷的巯基化在环境温度下在溶液中产生对密码子识别具有生物学意义的核苷的优选构象[Sierzputowska-Gracz，H.; Sochacka，E.; Malkiewicz，A.; Kuo，K.; Gehrke，C.; Agris，P. F. J. Am. 1987，109，7171-7177]。我们调查和比较，质子核磁共振（NMR）光谱，热力学稳定性的构象的2-硫代尿苷和5个生物重要的5位衍生物和6个类似的尿苷。在生理条件下，2-硫代尿苷的C（2 '）到C（3'）内跃迁的焓值比相应的非硫醇化尿苷大4.8倍，平均变化为1 kcal/mol，Δ-G，发现有利于C（3 '）内构象，优先发现在C（2'）内构象。通过对二核苷s2 UpU的分析，研究了相邻核苷对2-硫代尿苷和尿苷的结构和动力学的影响。在二核苷中，各个核苷在结构上和动力学上都与它们各自的单核苷没有区别。因此，2-位硫醇化而不是5-位修饰产生了明显更稳定、运动更受限的C（3 '）内、偏置加反构象异构体。这种生物学上优选的结构可能最适合于反密码子碱基堆积以及环和茎的稳定性。tRNA的结果是腺嘌呤作为唯一合适的密码子第三个碱基的修饰摆动选择。
Thiolation of transfer RNA wobble position uridines produces a preferred conformation of the nucleoside in solution at ambient temperature that is of biological significance to codon recognition [Sierzputowska-Gracz, H.; Sochacka, E.; Malkiewicz, A.; Kuo, K.; Gehrke, C.; Agris, P. F. J. Am. Chem. Soc. 1987,109, 7171-7177]. We investigated and compared, by proton nuclear magnetic resonance (NMR) spectroscopy, the thermodynamic stability of the conformations of 2-thiouridine and five biologically important 5-position derivatives and the six analogous uridines. Under physiological conditions, there were 4.8 times larger values of enthalpy and an average change of 1 kcal/mol, DELTA-G, for the C(2') to C(3') endo transitions of the 2-thiouridines, found to favor the C(3') endo conformation, than for the respective non-thiolated uridines, found preferentially in the C(2') endo conformation. The effect of an adjacent nucleoside on the structures and dynamics of 2-thiouridine and uridine was studied by analyzing the dinucleoside s2UpU. Within the dinucleoside the individual nucleosides neither differed in structure nor dynamics from their respective mononucleosides. Therefore, the 2-position thiolation, and not the 5-position modification, produced a significantly more stable, motionally more restricted, C(3') endo, gauche plus, anti conformer. This thermodynamically preferred structure may be best suited for anticodon base stacking and loop and stem stability. The result in tRNA is a modified-wobble selection of adenine as the only suitable third base of the codon.