Structure of the Arabidopsis thaliana NADPH-cytochrome P450 reductase 2 (ATR2) provides insight into its function
Structure of the Arabidopsis thaliana NADPH-cytochrome P450 reductase 2 (ATR2) provides insight into its function
复制标题
拟南芥 NADPH-细胞色素 P450 还原酶 2 (ATR2) 的结构有助于深入了解其功能
DOI：
10.1111/febs.14017
复制
发表时间：
2017-03-01
期刊：
影响因子：
5.4
通讯作者：
He, Yikun
中科院分区：
文献类型：
--
作者：
Niu, Guoqi;Zhao, Shun;He, Yikun
细胞色素P450家族成员催化多种单加氧酶反应，对于真核生物膜结合成员，NADPH通常用作还原剂。黄素蛋白NADPH-细胞色素P450还原酶（CPR）使电子通过其黄素辅助因子从NADPH转移到细胞色素P450。ATR2是模式植物拟南芥（Arabidopsis thaliana）基因组中两个真正的CPR基因之一，其产物已经获得了生理和动力学特征。本文报道了拟南芥nadph -细胞色素P450还原酶2 （ATR2）的2.3埃结构，发现这两种黄素辅因子的位置不同于其他已知的CPR结构。与可能的黄素电子转移相关的残基突变保留了ATR2的还原酶活性，这表明黄素之间存在直接的电子转移途径。相反，介导结构域间相互作用的单个残基（R708）突变消除了这种活性。由于该残基仅在植物CPRs中保守，我们推测在ATR2中观察到的植物特异性工作机制。
Members of the cytochrome P450 family catalyze a variety of mono-oxygenase reactions, and for the eukaryotic membrane-bound members, NADPH is typically used as the reducing agent. The flavoprotein NADPH-cytochrome P450 reductase (CPR) enables electron transfer from NADPH to cytochrome P450 via its flavin cofactors. ATR2 is one of the two authentic CPR genes in the genome of the model plant Arabidopsis thaliana, and its product has been physiologically and kinetically characterized. Here, we report the 2.3 angstrom structure of Arabidopsis thaliana NADPH-cytochrome P450 reductase 2 (ATR2) and find that the position of the two flavin cofactors differs from that of other known CPR structures. Mutation of residues related to possible interflavin electron transfer retains the reductase activity of ATR2, which suggests a direct electron transfer pathway between the flavins. In contrast, mutation of a single residue (R708) mediating interdomain interaction abolishes this activity. Because this residue is only conserved in plant CPRs, we speculate a plant-specific working mechanism as observed in ATR2.