Specificity in the binding of aminoglycosides to HIV-RRE RNA.
Specificity in the binding of aminoglycosides to HIV-RRE RNA.
复制标题
氨基糖苷类与 HIV-RRE RNA 结合的特异性。
DOI：
10.1021/bi990273a
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Rando,RR
中科院分区：
文献类型：
--
作者：
Cho,J;Rando,RR
我们对新霉素B与RRE结构体的结合进行了定量研究，以确定RNA中非watson Crick碱基配对元件与氨基糖苷结合之间的关系。RRE区域包含两个不配对的结构域，分别包含一个基底凸起和一个气泡结构。由于氨基糖苷结合的位点定位于泡区，单碱基凸起的缺失对新霉素的结合没有影响。将泡区转化为a型双链，在75倍的范围内以3 - 5倍的亲和力逐步消除新霉素B的结合。因此，氨基糖苷在RNA非双工结构域的结合是有利的，但氨基糖苷的结合只是分级特异性的，随着结构进一步偏离双工形式，亲和性逐渐增强。高亲和力的氨基糖苷结合很可能不会发生在双链RNA中，因为主槽太窄，不允许氨基糖苷进入，而结构扰动使槽变宽，从而促进了进入。然而，这些相互作用仅在氨基糖苷结构和RNA结构域结构方面具有等级特异性。
Quantitative studies of the binding of neomycin B to RRE constructs are carried out to determine the relationship between non-Watson Crick base-paired elements in the RNA and aminoglycoside binding. The RRE region contains two unpaired domains containing a single base bulge and a bubble structure, respectively. Deletion of the single base bulge has no effect on neomycin binding as the site of aminoglycoside binding is localized to the bubble region. Converting the bubble region into an A-form duplex gradually abolishes neomycin B binding in 3−5-fold steps in affinity over a 75-fold range. Thus, the binding of aminoglycoside is favored at domains in RNA that are nonduplex in nature, but aminoglycoside binding is only graded-specific in that affinities are enhanced gradually as the structure further deviates from a duplex form. It is likely that high-affinity aminoglycoside binding does not occur in duplex RNA because the major groove is too narrow to allow for aminoglycoside access and that structural perturbations that allow widening of the groove facilitate access. However, these interactions are only graded-specific with respect to both aminoglycoside structure and RNA domain structure.