Reactive oxygen species are unstable molecules generated by the partial reduction of dioxygen. NADPH oxidases are a ubiquitous family of enzymes devoted to ROS production. They fuel an array of physiological roles in different species and are chemically demanding enzymes requiring FAD, NADPH and heme prosthetic groups in addition to either calcium or a various number of cytosolic mediators for activity. These activating partners are exclusive components that partition and distinguish the NOX members from one another. To gain insight into the evolution of these activating mechanisms, and in general in their evolutionary history, we conducted an in-depth phylogenetic analysis of the NADPH oxidase family in eukaryotes. We show that all characterized NOXs share a common ancestor, which comprised a fully formed catalytic unit. Regarding the activation mode, we identified calcium-dependency as the earliest form of NOX regulation. The protein-protein mode of regulation would have evolved more recently by gene-duplication with the concomitant loss of the EF-hands motif region. These more recent events generated the diversely activated NOX systems as observed in extant animals and fungi.

中文翻译：

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真核生物 NADPH 氧化酶家族的进化和结构分析揭示了最初的钙依赖性

活性氧是分子氧部分还原产生的不稳定分子。 NADPH 氧化酶是一个普遍存在的酶家族，专门用于产生 ROS。它们在不同物种中发挥一系列生理作用，并且是化学要求较高的酶，除了钙或各种细胞质介质外，还需要 FAD、NADPH 和血红素辅基来发挥活性。这些激活伙伴是区分和区分 NOX 成员的专有组件。为了深入了解这些激活机制的进化以及它们的总体进化史，我们对真核生物中的 NADPH 氧化酶家族进行了深入的系统发育分析。我们表明，所有特征化的氮氧化物都有一个共同的祖先，它包含一个完全形成的催化单元。关于激活模式，我们确定钙依赖性是 NOX 调节的最早形式。蛋白质-蛋白质调节模式最近通过基因复制以及伴随的 EF-hands 基序区域的丢失而进化。这些最近发生的事件产生了在现存动物和真菌中观察到的多种激活的氮氧化物系统。