Oz Gleenberg Iris, Herschhorn Alon, Goldgur Yehuda, Hizi Amnon
Department of Cell and Developmental Biology, The Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Arch Biochem Biophys. 2007 Feb 15;458(2):202-12. doi: 10.1016/j.abb.2006.12.007. Epub 2006 Dec 28.
Previous studies show that the reverse transcriptase (RT) of human immunodeficiency virus type-1 (HIV-1) and RT-derived peptides interact with and inhibit the viral integrase (IN). In the present study, we have performed the complementary study by screening a complete library of HIV-1 IN-derived peptides for their effects on the RT. We have identified a 20-residues long peptide, derived from the IN (residues 46-65) that binds the RT and inhibits its DNA-polymerase activities (without affecting the ribonuclease-H activity). The full 20-residues sequence is required for maximal inhibition. This inhibition is non-competitive and probably results from obstructing the formation of RT-DNA complexes by the peptide. The data and the molecular docking model presented suggest that this inhibition is probably caused by a steric hindrance or conformational changes of the RT. These results can facilitate the development of novel and specific peptide-based HIV-1 RT inhibitors that might help in the fight against AIDS.
先前的研究表明，人类免疫缺陷病毒1型（HIV-1）的逆转录酶（RT）及RT衍生肽可与病毒整合酶（IN）相互作用并抑制其活性。在本研究中，我们通过筛选完整的HIV-1 IN衍生肽文库对RT的影响进行了补充研究。我们鉴定出一种源自IN（第46 - 65位氨基酸）的20个氨基酸长的肽，它能结合RT并抑制其DNA聚合酶活性（不影响核糖核酸酶H活性）。最大抑制作用需要完整的20个氨基酸序列。这种抑制是非竞争性的，可能是由于该肽阻碍了RT-DNA复合物的形成。所呈现的数据和分子对接模型表明，这种抑制可能是由RT的空间位阻或构象变化引起的。这些结果有助于开发新型、特异性的基于肽的HIV-1 RT抑制剂，可能有助于抗击艾滋病。
