DNA Cleavage by a De Novo Designed Protein–Titanium Complex
DNA Cleavage by a De Novo Designed Protein–Titanium Complex
复制标题
通过 De Novo 设计的蛋白质钛复合物进行 DNA 切割
DOI：
10.1021/acs.inorgchem.0c01707
复制
发表时间：
2020
影响因子：
4.6
通讯作者：
Buettner, Katherine M.
中科院分区：
文献类型：
--
作者：
Paredes, Alexander;Loh, Brittany M.;Peduzzi, Olivia M.;Reig, Amanda J.;Buettner, Katherine M.
钛是地球上最丰富的元素之一，但由于其易水解，通常被认为在生物学中没有作用。自然界利用多种机制从水解中稳定硬路易斯酸性金属，为如何使用生物配体稳定钛提供了灵感。新设计的具有良好表征的Due Ferri单链（DFsc）蛋白用于结合和稳定铁，并提供一个具有硬路易斯碱残基的结合位点，能够结合两个金属离子。我们证明了DFsc支架稳定地结合了2等量的钛，并保护它们免受不必要的水解。测试了Ti4+ -DFsc蛋白复合物水解切割DNA的能力，发现它在一夜反应中使质粒DNA线性化。因此，Ti4+ -DFsc是第一个功能性、可溶性钛蛋白复合物的例子。
Titanium is one of the most abundant elements on Earth but is commonly thought to have no role in biology because of its propensity to hydrolyze. Nature stabilizes hard Lewis acidic metals from hydrolysis using a variety of mechanisms, providing inspiration for how titanium can be stabilized using biological ligands. The well-characterized Due Ferri single-chain (DFsc)de novodesigned protein was developed to bind and stabilize iron and provides a binding site with hard Lewis basic residues able to bind two metal ions. We demonstrate that the DFsc scaffold stably binds 2 equiv of titanium and protects them from unwanted hydrolysis. The Ti4+–DFsc protein complex was tested for its ability to hydrolytically cleave DNA, where it was seen to linearize plasmid DNA in an overnight reaction. Ti4+–DFsc is thus the first example of a functional, soluble titanium–protein complex.