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HIV-1反式激活蛋白(Tat蛋白)与TAR-RNA的结合被其L-对映体选择性抑制。

TAR-RNA binding by HIV-1 Tat protein is selectively inhibited by its L-enantiomer.

作者信息

Garbesi A, Hamy F, Maffini M, Albrecht G, Klimkait T

机构信息

Consiglio Nazionale delle Ricerche, I. Co. C.E.A., Bologna, Italy and Novartis Pharma Research,Department of Oncology, K-125 3.09, CH-4002 Basle, Switzerland.

出版信息

Nucleic Acids Res. 1998 Jun 15;26(12):2886-90. doi: 10.1093/nar/26.12.2886.

Abstract

An oligoribonucleotide, corresponding to the Tat-interactive top half of the HIV-1 TAR RNA stem-loop, was synthesized in both the natural D- and the enantiomeric L-configurations. The affinity of Tat for the two RNAs, assessed by competition binding experiments, was found to be identical and is reduced 10-fold for both, upon replacement of the critical bulge residue U23 with cytidine. It is suggested that this interaction of the flexible Tat protein depends strongly upon the tertiary structure of a binding pocket within TAR, but not upon its handedness, and may be described by a 'hand-in-mitten' model.

摘要

合成了一种寡核糖核苷酸,其对应于HIV-1 TAR RNA茎环中与Tat相互作用的上半部分,分别采用天然的D构型和对映体L构型。通过竞争结合实验评估Tat对这两种RNA的亲和力,发现二者相同,并且当关键的凸起残基U23被胞嘧啶取代时,两者的亲和力均降低了10倍。这表明柔性Tat蛋白的这种相互作用很大程度上取决于TAR内结合口袋的三级结构,而不取决于其手性,并且可以用“手套-手”模型来描述。

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