美国麻省理工学院霍华德•休斯医学院Catherine L. Drennan和麻省理工学院生物系JoAnne Stubbe小组合作宣布他们解析了核糖核苷酸还原酶（RNR）全酶复合物中捕获自由基转移途径的结构。2020年3月26日，国际学术期刊《科学》在线发表了这一成果。

在本研究中，研究人员使用双取代的β2，E52Q /（2,3,5）-三氟酪氨酸122-β2来捕获稳定α2β2复合中的野生型α2。 研究人员通过冷冻电镜获得了该复合物分辨率为3.6Å的结构，从而实现了活跃RNR长32Å自由基转移途径的结构可视化。

据了解，RNR是一个多样的酶家族，它们单独能够从头产生2'-脱氧核苷酸，因此对于DNA生物合成和修复至关重要。所有RNR催化的核苷酸还原反应都需要生成一个瞬时的活性位点：硫基自由基；而在I型RNR中，该过程涉及α和β两个亚基之间远距离的自由基转移。由于亚基的瞬态结合，难以获得活性α2β2 RNR复合物的原子结构。

附：英文原文

Title: Structure of a trapped radical transfer pathway within a ribonucleotide reductase holocomplex

Author: Gyunghoon Kang, Alexander T. Taguchi, JoAnne Stubbe, Catherine L. Drennan

Issue&Volume: 2020/03/26

Abstract: AbstractRibonucleotide reductases (RNRs) are a diverse family of enzymes that are alone capable of generating 2′-deoxynucleotides de novo and are thus critical in DNA biosynthesis and repair. The nucleotide reduction reaction in all RNRs requires the generation of a transient active site thiyl radical, and in class I RNRs this process involves a long-range radical transfer between two subunits, α and β. Due to the transient subunit association, an atomic resolution structure of an active α2β2 RNR complex has been elusive. Here we use a doubly-substituted β2, E52Q/(2,3,5)-trifluorotyrosine122-β2 to trap wildtype-α2 in long-lived α2β2 complex. We report the structure of this complex by cryo-electron microscopy to 3.6- resolution, allowing for structural visualization of a 32--long radical transfer pathway that affords RNR activity.

DOI: 10.1126/science.aba6794

Source: https://science.sciencemag.org/content/early/2020/03/25/science.aba6794