On base flipping
On base flipping
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DOI：
10.1016/0092-8674(95)90046-2
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发表时间：
1995-07
期刊：
影响因子：
64.5
通讯作者：
R. Roberts
中科院分区：
文献类型：
--
作者：
R. Roberts
虽然变化和适应是生命的关键，但大自然不愿意放弃旧的发明。即使在今天，当我们祖先的假设RNA世界已经被蛋白质提供的更丰富的可能性所取代时，我们仍然发现RNA催化的关键过程。也许最古老的发现是碱基配对的独特力量，使复制成为可能。这一定是RNA世界发展的关键，也是让DNA成为现代遗传物质的关键。今天的生活充满了古代过程的其他例子，这些过程完好无损地存在或只经历了微妙的修改。最近才发现的一个发明是DNA中的碱基翻转（Klimasauskas等人，1994年）。胞嘧啶化DNA甲基转移酶M催化机制的一个关键特征。Hhal涉及将目标胞嘧啶180从DNA螺旋中翻转到酶中的口袋中。最近的晶体学证据表明，其他酶也可能从DNA中翻转出碱基。在这篇简短的评论中，我提出碱基翻转是进化过程中的一个早期发现，而DNA仍被作为遗传物质进行测试，这将反映在这种机制比迄今报道的更广泛的发生。胞嘧啶-5 DNA甲基转移酶当DNA胞嘧啶甲基转移酶M。HhaI（识别序列，GMeCGC）与其底物DNA相互作用，靶胞嘧啶完全从螺旋中翻转出来并进入酶中的空腔中，在该空腔中发生催化化学（图1）（Klimasauskas等人，1994年）。DNA结构中这种戏剧性但优雅的扭曲与其他蛋白质结合时诱导的扭结和弯曲形成鲜明对比（Pabo和Sauer，1992）。值得注意的是，在这个碱基翻转过程中不需要外部能量供应，因为它只在蛋白质、DNA和辅因子S-腺苷甲硫氨酸的存在下发生。
Although change and adaptation are key to life, nature is reluctant to abandon old inventions. Even today when the hypothetical RNA world of our ancestors has been supplanted by the richer possibilities offered by proteins, we still find key processes catalyzed by RNA. Perhaps the oldest discovery was the unique power of base pairing to enable replication. This must have been key to the development of the RNA world and of equal importance in allowing DNA to become the modern genetic material. Life today is full of other examples of ancient processes that exist intact or have undergone only subtle modifications. One invention that has only recently been found is base flipping in DNA (Klimasauskas et al., 1994). A key feature of the catalytic mechanism of the cytosined DNA methyltransferase M. Hhal involves flipping the target cytosine 180 out of the DNA helix into a pocket in the enzyme. Recent crystallographic evidence suggests that other enzymes may also flip bases out of DNA. In this minireview I propose that base flipping was an early discovery during evolution, while DNA was still being tested as the genetic material, and that this will be reflected by the more widespread occurrence of this mechanism than has been reported to date.Cytosine-5 DNA Methyltransferases When the DNA cytosined methyltransferase M. Hhal (recognition sequence, GMeCGC) interacts with its substrate DNA, the target cytosine is flipped completely out of the helix and into a cavity in the enzyme where the chemistry of catalysis takes place (Figure 1)(Klimasauskas et al., 1994). This dramatic but elegant distortion in the DNA structure contrasts sharply with the kinks and bends induced by other proteins upon binding (Pabo and Sauer, 1992). Remarkably, there is no external energy supply required during this base flipping process since it takes place in the presence of only protein, DNA, and the cofactor S-adenosylmethionine.