Institute of Chinese Minority Traditional Medicine, Minzu University of China , Beijing 100081, People's Republic of China.
J Phys Chem B. 2012 Apr 26;116(16):4801-11. doi: 10.1021/jp300307u. Epub 2012 Apr 17.
A recent finding of a bacterial strain (GFAJ-1) that can rely on arsenic instead of phosphorus raised the questions of if and how arsenate can replace phosphate in biomolecules that are essential to sustain cell life. Apart from questions related to chemical stability, there are those of the structural and functional consequences of phosphate-arsenate substitutions in vital nucleotides in GFAJ1-like cells. In this study we selected three types of molecules (ATP/ADP as energy source and replication regulation; DNA-protein complexes for DNA replication and transcription initiation; and a tRNA-protein complex and ribosome for protein synthesis) to computationally probe if arsenate nucleotides can retain the structural and functional features of phosphate nucleotides. Hydrolysis of adenosine triarsenate provides 2-3 kcal/mol less energy than ATP hydrolysis. Arsenate DNA/RNA interacts with proteins slightly less strongly than phosphate DNA/RNA, mainly due to the weaker electrostatic interactions of arsenate. We observed that the weaker arsenate RNA-protein interactions may hamper rRNA assembly into a functional ribosome. We further compared the experimental EXAFS spectra of the arsenic bacteria with theoretical EXAFS spectra for arsenate DNA and rRNA. Our results demonstrate that while it is possible that dried GFAJ-1 cells contain linear arsenate DNA, the arsenate 70S ribosome does not contribute to the main arsenate depository in the GFAJ-1 cell. Our study indicates that evolution has optimized the inter-relationship between proteins and DNA/RNA, which requires overall changes at the molecular and systems biology levels when replacing phosphate by arsenate.
最近发现的一种细菌（GFAJ-1）可以依赖砷而不是磷，这引发了一些问题，即砷酸盐是否可以替代对维持细胞生命至关重要的生物分子中的磷酸盐，以及在 GFAJ1 样细胞中的重要核苷酸中，磷酸盐-砷酸盐取代的结构和功能后果。在这项研究中，我们选择了三种类型的分子（ATP/ADP 作为能量来源和复制调节；用于 DNA 复制和转录起始的 DNA-蛋白质复合物；以及 tRNA-蛋白质复合物和核糖体用于蛋白质合成），以计算探测砷酸盐核苷酸是否可以保留磷酸盐核苷酸的结构和功能特征。三砷腺苷的水解比 ATP 水解提供的能量少 2-3 千卡/摩尔。砷酸盐 DNA/RNA 与蛋白质的相互作用比磷酸盐 DNA/RNA 略弱，主要是由于砷酸盐的静电相互作用较弱。我们观察到较弱的砷酸盐 RNA-蛋白质相互作用可能会阻碍 rRNA 组装成功能性核糖体。我们进一步比较了砷细菌的实验 EXAFS 光谱与理论上的砷酸盐 DNA 和 rRNA 的 EXAFS 光谱。我们的结果表明，虽然 GFAJ-1 细胞可能含有线性砷酸盐 DNA，但砷酸盐 70S 核糖体不会对 GFAJ-1 细胞中的主要砷酸盐储存库做出贡献。我们的研究表明，进化已经优化了蛋白质与 DNA/RNA 之间的相互关系，当用砷酸盐替代磷酸盐时，这需要在分子和系统生物学水平上进行全面的改变。
