Alteration of the oxygen-dependent reactivity of de novo Due Ferri proteins.
Alteration of the oxygen-dependent reactivity of de novo Due Ferri proteins.
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作者：
从头蛋白提供了一个独特的机会来研究金属蛋白的结构与功能的关系，在一个最小的，明确的，可控的支架。在这里，我们描述了一种从头设计的来自Due Ferri家族的双铁羧酸盐蛋白的功能的合理编程。该蛋白质最初是为了催化对苯二酚的氧依赖的双电子氧化而创建的，后来通过重塑底物访问腔并在金属结合腔中引入关键的第三His配体来催化芳胺的选择性N-羟基化。为了稳定蛋白质核心中的组氨酸配体，还需要额外的第二和第三壳修饰。这些变化导致两种反应的相对速率至少增加了106倍。这一结果突出了将从头蛋白用作支架的潜力，用于未来研究影响双铁活性中心催化调节的几何和电子因素。
De novo proteins provide a unique opportunity for investigating the structure-function relationships of metalloproteins in a minimal, well-defined, and controlled scaffold. Herein, we describe the rational programming of function in a de novo designed di-iron carboxylate protein from the due ferri family. Originally created to catalyze O2-dependent, two-electron oxidation of hydroquinones, the protein was reprogrammed to catalyze the selective N-hydroxylation of arylamines by remodeling the substrate access cavity and introducing a critical third His ligand to the metal binding cavity. Additional second-and third-shell modifications were required to stabilize the His ligand in the core of the protein. These changes resulted in at least a 106 –fold increase in the relative rates of the two reactions. This result highlights the potential for using de novo proteins as scaffolds for future investigations of geometric and electronic factors that influence the catalytic tuning of di-iron active sites.
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影响因子：
15
作者：
Korboukh, Victoria Korneeva;Li, Ning;Barr, Eric W.;Bollinger, J. Martin, Jr.;Krebs, Carsten
通讯作者：
Krebs, Carsten
影响因子：
5.6
作者：
Calhoun, JR;Kono, H;Saven, JG
通讯作者：
Saven, JG
影响因子：
2.9
作者：
Calhoun, JR;Nastri, F;DeGrado, WF
通讯作者：
DeGrado, WF
DOI：
10.1039/j29690000823
发表时间：
1969-01-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY B-PHYSICAL ORGANIC
影响因子：
--
作者：
CORBETT, JF
通讯作者：
CORBETT, JF
DOI：
10.1073/pnas.0404387101
发表时间：
2004-08-10
影响因子：
11.1
作者：
Kaplan, J;DeGrado, WF
通讯作者：
DeGrado, WF