Laboratory of Computational Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Laboratory of Computational Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Biophys J. 2024 Jun 18;123(12):1648-1653. doi: 10.1016/j.bpj.2024.05.007. Epub 2024 May 9.
DNA primase is an iron sulfur enzyme in DNA replication responsible for synthesizing short RNA primers that serve as starting points for DNA synthesis. The role of the [4Fe-4S] cluster is not well determined. Here, we calculate the redox potential of the [4Fe-4S] with and without DNA/RNA using continuum electrostatics. In addition, we identify the structural changes coupled to the oxidation/reduction. Our calculations show that the DNA/RNA primer lowers the redox potential by 110 and 50 mV for the [4Fe-4S] and [4Fe-4S] states, respectively. The oxidation of the cluster is coupled to structural changes that significantly reduce the binding energies between the DNA and the nearby residues. The negative charges accumulated by the DNA and the RNA primers induce the oxidation of the [4Fe-4S] cluster. This in turn stimulates structural changes on the DNA-protein interface that significantly reduce the binding energies.
DNA 引物酶是 DNA 复制中的一种铁硫酶，负责合成短的 RNA 引物，作为 DNA 合成的起点。[4Fe-4S] 簇的作用尚未确定。在这里，我们使用连续静电场计算了有和没有 DNA/RNA 时[4Fe-4S]的氧化还原电位。此外，我们确定了与氧化/还原相关的结构变化。我们的计算表明，DNA/RNA 引物分别将[4Fe-4S]和[4Fe-4S]状态的氧化还原电位降低了 110 和 50 mV。簇的氧化与结构变化相关，这显著降低了 DNA 与附近残基之间的结合能。DNA 和 RNA 引物上积累的负电荷诱导[4Fe-4S]簇的氧化。这反过来又刺激了 DNA-蛋白质界面上的结构变化，显著降低了结合能。
