A transposition of the reverse transcriptase gene reveals unexpected structural homology to E. coli DNA polymerase I.
A transposition of the reverse transcriptase gene reveals unexpected structural homology to E. coli DNA polymerase I.
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逆转录酶基因的转座揭示了与大肠杆菌 DNA 聚合酶 I 意想不到的结构同源性。
作者：
Taylor,EW;Jaakkola,J
对人类免疫缺陷病毒（HIV）逆转录酶（RT）的结构有更深入的了解，将极大地有助于合理设计靶向逆转录酶的抗病毒药物。coliDNA聚合酶I （Pol I）一直被认为局限于几个小区域，这表明同源分子模型的基础很小。然而，我们发现RT聚合酶结构域C端的一个区域与Pol I的中心区域同源，该区域位于通用聚合酶基序a和C之间（具体来说，是Pol I晶体结构的N-O-P螺旋）；单个转位将RT和Pol I基因紧密地对齐，揭示了具有20%残基同一性的相似结构域结构，以及几种rna依赖性聚合酶基序的可能结构相关性。黄粘球菌（一种被认为在20亿年前从其他物种分化出来的细菌）的RT，如果同样转位，则显示出与HIV-1和e的同源性。这表明RT和Pol I聚合酶基因之间可能存在非常古老的分歧。第二个更重要的匹配。coliregion是在逆转录病毒核糖核酸酶H （RNase H）结构域中被发现的，并且精确地对应于先前研究人员与theE对齐的区域。表明Pol I螺旋O和P分别与RNase H晶体结构的A和D螺旋同源。这些结果与分子进化的模块化理论相一致。
The rational design of antiviral agents targeting the reverse transcriptase (RT) of the human immunodeficiency virus (HIV) would greatly benefit from a more intimate knowledge of the structure of RT. Until now, the degree of sequence similarity between RT andE. coliDNA polymerase I (Pol I) has been thought to be confined to several small regions, suggesting little basis for homology molecular modeling. However, we have found that a region in the C terminal of the RT polymerase domain is homologous to a central region of Pol I that lies between the universal polymerase motifs A and C (specifically, helices N-O-P of the Pol I crystal structure); a single transposition closely aligns the RT and Pol I genes, revealing a similar domain structure with 20% residue identity, as well as the possible structural correlates of several RNA-dependent polymerase motifs. The RT fromMyxococcus xanthus(a bacterium believed to have diverged from other species 2 billion years ago), if similarly transposed, shows homology to both HIV-1 andE. coli, suggesting the possibility of a very ancient divergence between the RT and Pol I polymerase genes. A second even more significant match to thisE. coliregion was found in the retroviral ribonuclease H (RNase H) domain, and corresponds precisely to a region that has been aligned by previous investigators with theE. coliRNase H, suggesting that Pol I helices O and P are homologous to helices A and D of the RNase H crystal structure, respectively. These results are consistent with a modular theory of molecular evolution.