An unexpected major groove binding of netropsin and distamycin A to tRNA(phe).
An unexpected major groove binding of netropsin and distamycin A to tRNA(phe).
复制标题
netropsin 和偏端霉素 A 与 tRNA(phe) 发生意外的大沟结合。
DOI：
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发表时间：
1984
影响因子：
4.4
通讯作者：
M. Sundaralingam
中科院分区：
文献类型：
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作者：
J. Rubin;M. Sundaralingam
通过将药物扩散到tRNA晶体中，制备了酵母tRNA（phe）与寡肽抗生素netropsin和偏端霉素A的晶体复合物。这些复合物的X-射线结构分析揭示了两种药物的单一共同结合位点，其位于tRNA T-茎的主要或深沟中。netropsin-tRNA复合物通过药物的酰胺基团与一条链上的tRNA碱基G51 O（6）、U 52 O（4）和G53 N（7）之间的特异性氢键稳定，并且通过药物的带正电荷的胍基侧链和同一链上的磷酸tRNA P53与带正电荷的脒基丙基侧链和磷酸tRNA P53之间的静电相互作用而进一步稳定。在双螺旋的相对链上磷酸P61、P62和P63。这些结果与这些药物与DNA中的非鸟嘌呤序列的牵连小沟结合相反。与tRNA中GUG序列的结合意味着大沟与某些DNA序列的结合是可能的。
Crystalline complexes of yeast tRNA(phe) and the oligopeptide antibiotics netropsin and distamycin A were prepared by diffusing drugs into crystals of tRNA. X-ray structure analyses of these complexes reveal a single common binding site for both drugs which is located in the major or deep groove of the tRNA T-stem. The netropsin-tRNA complex is stabilized by specific hydrogen bonds between the amide groups of the drug and the tRNA bases G51 O(6), U52 O(4) and G53 N(7) on one strand, and is further stabilized by electrostatic interactions between the positively charges guanidino side chain of the drug and the tRNA phosphate P53 on the same strand and the positively charged amidino propyl side chain and the phosphates P61, P62 and P63 on the opposite strand of the double helix. These results are in contrast to the implicated minor groove binding of these drugs to non-guanine sequences in DNA. The binding to the GUG sequence in tRNA implies that major groove binding to certain DNA sequences is possible.