Characterization of a folding intermediate from HIV-1 ribonuclease H
Characterization of a folding intermediate from HIV-1 ribonuclease H
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DOI：
10.1002/pro.5560071014
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发表时间：
1998-10-01
期刊：
影响因子：
8
通讯作者：
Marqusee, S
中科院分区：
文献类型：
--
作者：
Kern, G;Handel, T;Marqusee, S
来自HIV-1的RNA酶H结构域（HIV RNA酶H）编码基本的逆转录病毒活性。重折叠分离的HIV RNA酶H结构域显示了一个动力学中间体，可通过停流远紫外圆二色性和脉冲标记H/D交换检测。在该中间体中，链1、4和5以及螺旋A和D似乎是结构化的。与来自大肠杆菌的同源物相比，HIV RNA酶H的重折叠的限速步骤似乎更接近天然状态。我们已经使用缺乏螺旋E的C-末端缺失片段模拟了这种动力学中间体。与动力学中间体一样，该变体快速折叠并显示稳定性降低。我们认为抑制螺旋E与折叠中间体的对接可能是抗HIV-1治疗的一种新策略。
The RNase H domain from HIV-1 (HIV RNase H) encodes an essential retroviral activity. Refolding of the isolated HIV RNase H domain shows a kinetic intermediate detectable by stopped-flow far UV circular dichroism and pulse-labeling H/D exchange. In this intermediate, strands 1, 4, and 5 as well as helices A and D appear to be structured. Compared to its homolog from Escherichia coli, the rate Limiting step in refolding of HIV RNase H appears closer to the native state. We have modeled this kinetic intermediate using a C-terminal deletion fragment lacking helix E. Like the kinetic intermediate, this variant folds rapidly and shows a decrease in stability. We propose that inhibition of the docking of helix E to this folding intermediate may present a novel strategy for anti HIV-1 therapy.