From microbiology to cancer biology: the Rid protein family prevents cellular damage caused by endogenously generated reactive nitrogen species.
From microbiology to cancer biology: the Rid protein family prevents cellular damage caused by endogenously generated reactive nitrogen species.
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DOI：
10.1111/mmi.12945
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发表时间：
2015-04
影响因子：
3.6
通讯作者：
Ernst DC
中科院分区：
文献类型：
--
作者：
Downs DM;Ernst DC
Rid 蛋白家族高度保守并广泛分布于生命领域。主要针对肠道沙门氏菌的遗传和生化研究已经确定了 RidA 在响应内源性反应性代谢物中的作用。数据显示，2-氨基丙烯酸酯 (2AA) 是一种由一些吡哆醛 5'-磷酸 (PLP) 依赖性酶产生的反应性烯胺中间体，在没有 RidA 的情况下会积累。 2AA 的积累会导致参与重要代谢过程的几种酶的共价修饰和失活。这篇综述描述了 RidA 的 2AA 水解活性以及该生化活性对代谢网络的影响，从而影响生物体的适应性。报道的 RidA 活性以及 RidA 缺失时在体内遇到的后果挑战了酶学、生物化学和细胞代谢中关于瞬时生成的反应性烯胺中间体命运的基本假设。目前对沙门氏菌中 RidA 的了解以及 Rid 家族蛋白的广泛分布为未来研究定义 Rid 家族成员（从微生物到人类）的代谢作用提供了令人兴奋的机会。
The Rid family of proteins is highly conserved and broadly distributed throughout the domains of life. Genetic and biochemical studies, primarily in Salmonella enterica, have defined a role for RidA in responding to endogenously generated reactive metabolites. The data show that 2-aminoacrylate (2AA), a reactive enamine intermediate generated by some pyridoxal 5′-phosphate (PLP)-dependent enzymes, accumulates in the absence of RidA. The accumulation of 2AA leads to covalent modification and inactivation of several enzymes involved in essential metabolic processes. This review describes the 2AA hydrolyzing activity of RidA and the effect of this biochemical activity on the metabolic network, which impacts organism fitness. The reported activity of RidA and the consequences encountered in vivo when RidA is absent have challenged fundamental assumptions in enzymology, biochemistry and cell metabolism regarding the fate of transiently-generated reactive enamine intermediates. The current understanding of RidA in Salmonella and the broad distribution of Rid family proteins provide exciting opportunities for future studies to define metabolic roles of Rid family members from microbes to man.